Analysis of solute carrier organic anion transporter family member 1b1 and apolipoprotein E genes in a population from southern Yunnan / 中国基层医药

Objective:To analyze the distribution of solute carrier organic anion transporter family member 1b1 ( SLCO1B1) and apolipoprotein E ( ApoE) genes in a population from southern Yunnan. Methods:The data of 104 patients who received treatment in Southern Central Hospital of Yunnan Province (The First People's Hospital of Honghe State) between May 2019 and June 2020 were collected. The distribution of SLCO1B1 and ApoE genes and their relationship with nationality, sex, and age were analyzed and compared between different regions. Results:The percentage of patients carrying *1a/*1a, *1a/*1b, *1b/*1b, *1a/*15, *1b/*15, five phenotypes of SLCO1B1 gene, in the population from southern Yunnan was 4.81%, 32.69%, 42.31%, 12.50% and 7.69% respectively. Phenotypes *1a/*5, *5/*5, *5/*15 and *15/*15 were not detected. Normal metabolic phenotype of SLCO1B1 accounted for 79.81%, and intermediate metabolic phenotype of SLCO1B1 accounted for 20.19%. Weak metabolic phenotype was not detected. The percentage of patients carrying E2/E2, E2/E3, E3/E3, E3/E4, E4/E4, five phenotypes of ApoE gene in the population from southern Yunnan was 0.96%, 16.35%, 70.19%, 11.54% and 0.96% respectively. E2/E4 phenotype was not detected. The percentage of patients with ApoE protective phenotype, ApoE normal phenotype, and ApoE risk phenotype was 17.31%, 70.19% and 12.50% respectively. The observed polymorphism mutation frequency of SLCO1B1 and ApoE genes was consistent with the Hardy-Weinberg equilibrium ( P > 0.05), suggesting constancy and a population representation. The Fisher test showed that SLCO1B1 gene distribution differed significantly between ethnic minorities and Han nationality in southern Yunnan ( P = 0.013). There was no significant difference in SLCO1B1 gene distribution between different sexes and between different ages (all P > 0.05). There was no significant difference in ApoE gene distribution between ethnic minorities and Han nationality, between different sexes, and between different ages in the population from southern Yunnan (all P > 0.05). Conclusion:SLCO1B1 gene distribution is related to nationality in the population from southern Yunnan, but it is unrelated to sex and age. ApoE gene distribution is unrelated to nationality, sex and age.

Analysis and clinical significance of cytochrome P 450 2C19 gene in patients with cardiovascular and cerebrovascular diseases in southern Yunnan / 中国基层医药

Objective:To analyze the distribution and clinical significance of cytochrome P 450 2C19 (CYP2C19) gene in patients with cardiovascular and cerebrovascular diseases in southern Yunnan. Methods:The data of 245 patients with cardiovascular and cerebrovascular diseases who received treatment in Southern Central Hospital of Yunnan Province between May 2019 and June 2020 were retrospectively analyzed. The distribution of CYP2C19 gene and its relationship with nationality, age, sex, blood lipids, hypertension, and diabetes were analyzed and compared between southern Yunnan and other regions.Results:The proportions of seven phenotypes of CYP2C19 gene *1/*17, *1/*1, *1/*2, *1/*3, *2/*2, *2/*3, *3/*3 in 245 patients were 2.86%, 38.37%, 39.18%, 5.31%, 9.39%, 4.08% and 0.82%, respectively. The proportions of individuals with superfast/ultrafast metabolism, fast metabolism, intermediate metabolism, and slow metabolism in 245 patients were 2.86%, 38.37%, 44.49%, and 14.29%, respectively. The frequency of polymorphisms in the CYP2C19 gene was consistent with the Hardy-Weinberg equilibrium ( P > 0.05), which was constant and representative. The Fisher test showed that the CYP2C19 gene distribution of patients with cardiovascular and cerebrovascular diseases in southern Yunnan was not greatly correlated with nationality, age, sex, underlying disease, blood lipids, and the types of cardiovascular and cerebrovascular diseases (all P > 0.05). There was a significant difference in CYP2C19 gene distribution in patients from southern Yunnan versus Dongguan, Jiangxi, Fujian, northern Sichuan, Chifeng, Xiamen, Shaanxi, and Kunming ( P < 0.001, < 0.001, 0.045, 0.008, 0.001, 0.005, < 0.001, 0.016). Conclusion:The distribution of CYP2C19 gene in patients with cardiovascular and cerebrovascular diseases in southern Yunnan is not obviously correlated with nationality, age, sex, underlying diseases, blood lipids, and the types of cardiovascular and cerebrovascular diseases. CYP2C19 gene distribution is related to regional distribution, which can guide personalized medication in different regions.

Polymorphism analysis on the 5′ flanking region of CD25 gene of Han males in naturally high radiation background area / 中国职业医学

OBJECTIVE: To explore the distribution characteristics of single nucleotide polymorphism(SNP) rs7072793 and rs3118470 in the 5′ flanking region of(cluster of differentiation 25, CD25) gene in Han males in the naturally high radiation background area(HBRA). METHODS: A random sampling method was used to select 48 and 51 healthy Han males from Tangkou town(HBRA group) in Yangjiang City and Hengpo town(control group) in Enping City, respectively, as the study subjects. The molecular mass array method was used to classify the genotype of the SNP sites rs7072793 and rs3118470 of CD25 gene in these subjects. The distribution difference of the alleles and genotypes was analyzed in individuals of these two groups. The allele frequency of HBRA population was compared with the distribution data of different populations in the Human Genome Project.RESULTS: The distribution of allele frequencies of rs7072793 and rs3118470 in both groups were consistent with the H-W equilibrium law of genetics(all P>0.05). In the HBRA group, variant allele C(58.3%) and genotype TC(50.0%) were dominant at rs7072793, wild-type allele T(55.2%) and genotype TC(56.2%) were dominant at rs3118470. There was no significant difference in the allele and genotype distributions between these two groups(all P>0.05). There was a difference of rs7072793 in the HBRA group compared to that of African and European populations, and rs3118470 in the HBRA group compared with the allele distribution frequencies in Africa, Europe and America populations(all P<0.05). CONCLUSION: In the male population of Han nationality in Yangjiang HBRA area, the alleles of rs7072793 and rs3118470 in the 5′ flanking region of CD25 gene were mainly C and T, respectively, and the genotypes were mainly TC. These two loci may have high genetic variability.

Influence of nutritional factors and the PON1 C(-107)T polymorphism on paraoxonase-1 activity in childhood / Influência de fatores nutricionais e do polimorfismo PON1 C(-107)T sobre a atividade da Paraoxonase 1 na infância

Abstract Objective: The cardioprotective enzyme paraoxonase-1 (PON1) suffers an important influence from genetic polymorphisms and nutritional factors. The aim of this study was to investigate the influence of diet, nutritional status, and the C(-107)T polymorphism on PON1 arylesterase activity in children. Methods: This was a cross-sectional study with 97 children, aged between 5 and 8 years, of both genders, from a pediatric outpatient clinic in southern Brazil. A sociodemographic, behavioral, and food consumption questionnaire was applied, and anthropometric measurements and laboratory blood samples were taken. PON1 arylesterase activity was measured by phenol extinction (U/mL), and DNA extraction and analysis of the PON1 C(-107)T polymorphism were performed. The Hardy-Weinberg equilibrium was tested with the chi-squared test and linear regression was used to estimate PON1 activity according to four adjustment models, with an acceptable error of 5%. Results: In the sample, the male gender accounted for 50.5%, 39.2% were 6 years of age, 54.5% had normal weight, and 51.5% had PON1 activity below the median (90.0, 15-30 U/mL). Genotype frequency was 54.6% (53/97), 31.0% (30/97), and 14.4% (14/97), respectively, for CT, CC, and TT, consistent with the Hardy-Weinberg equilibrium (p = 0.22). In the regression analysis, the model that included sociodemographic variables as well as frequency of consumption of fruits, vegetables, legumes, dairy products, and beans estimated a variability of 14.8% in PON1 activity combined with the PON1 C(-107)T polymorphism. Conclusions: During childhood, a good-quality diet with greater inclusion of healthy foods was important to predict the activity of the cardioprotective enzyme PON1 combined with the C(-107)T polymorphism of the PON1 gene.

Resumo Objetivo: A enzima cardioprotetora Paraoxonase 1 (PON1) sofre importante influência de polimorfismos genéticos e fatores nutricionais. O objetivo deste estudo foi investigar a influência da alimentação, do estado nutricional e do polimorfismo C(-107)T sobre a atividade arilesterase da PON1 em crianças. Métodos: Estudo transversal com 97 crianças entre 5 e 8 anos, de ambos os sexos, de um ambulatório de pediatria no sul do Brasil. Realizou-se questionário sociodemográfico, de comportamento e de consumo alimentar, medidas antropométricas e coleta de sangue em laboratório. A atividade arilesterase da PON1 foi mensurada pela extinção de fenol (U/mL), realizada extração do DNA e análise do polimorfismo PON1 C(-107)T. O equilíbrio de Hardy-Weinberg foi testado com qui-quadrado e usada regressão linear para estimar a atividade da PON1 segundo quatro modelos de ajuste, erro aceitável de 5%. Resultados: Na amostra o sexo masculino representou 50,5%, 39,2% tinham 6 anos, 54,5% eram eutróficos e 51,5% tinha atividade da PON1 inferior à mediana (90,0;15-30 U/ml). A frequência dos genótipos foi 54,6% (53/97), 31,0% (30/97) e 14,4% (14/97), respectivamente, para CT, CC e TT, estiveram em equilíbrio de Hardy-Weinberg (p = 0,22). Na análise de regressão o modelo que incluiu variáveis sociodemográficas, de frequência do consumo de frutas, verduras, legumes, laticínios e feijões estimou uma variabilidade de 14,8% na atividade da PON1 combinada ao polimorfismo PON1 C(-107)T. Conclusões: Na infância uma alimentação de boa qualidade, com maior participação de alimentos saudáveis foi importante para predizer a atividade da enzima cardioprotetora PON1 combinada ao polimorfismo C(-107)T do gene da PON1.

Polimorfismo +405G> C del gen del factor de crecimiento de endotelio vascular en población cubana / Vascular Endothelial Growth Factor gene +405G> C polymorphism in the Cuban population

Introducción: El factor de crecimiento endotelial vascular (VEGF) es una proteína involucrada en la proliferación y migración celular del endotelio vascular, en cuyo gen se ha reportado el polimorfismo +405G>C. Se reconoce que no existen reportes genéticos poblacionales de esta variante en Cuba, que permitan caracterizar los perfiles inmunogenéticos a nivel molecular, para su aplicación en estudios de asociación alélica. Objetivo: Describir las frecuencias génicas y genotípicas del polimorfismo VEGF (+405 G>C) en la población cubana. Material y Métodos: Se realizó un estudio observacional, descriptivo, transversal, entre octubre de 2017 y marzo de 2018 en 162 neonatos cubanos, de ambos sexos y sanos, para el pesquisaje neonatal de enfermedades metabólicas, cuyas muestras biológicas se conservaban en el banco de ADN del Centro Nacional de Genética Médica. La caracterización molecular de los genotipos fue realizada mediante un PCR-ARMS. Se utilizó el software GENEPOP 4.4 y el paquete estadístico STATISTICA 8.0 para los cálculos de las frecuencias génicas y genotípicas. Resultados: La población no se ajustó al modelo de equilibrio de Hardy Weinberg para el gen evaluado. Las frecuencias génicas estimadas para el polimorfismo VEGF (+405 G>C) fueron de 0,33 para el alelo G y de 0,67 para el alelo C. El cálculo de las frecuencias genotípicas resultó en 0,14, 0,37 y 0,49, para las variantes GG, GC y CC, respectivamente. Conclusiones: Las frecuencias alélicas VEGF.C fueron superiores a la del alelo VEGF.G, siendo el genotipo VEGF.GG el de menor representación en el conjunto estudiado(AU)

Introduction: The vascular endothelial growth factor (VEGF) is a protein involved in the proliferation and cell migration of the vascular endothelium. In its gene, +405G>C Polymorphism has been reported. There are no population genetic reports of this variant in Cuba that allow the characterization of immunogenetic profiles at a molecular level for its application to allelic association studies. Objectives: To describe the genic and genotypic frequencies of the VEGF (+405 G>C) polymorphism in the Cuban population. Material and Methods: A descriptive cross-sectional observational study was carried out from October 2017 to March 2018 in 162 Cuban healthy newborns of both sexes for the neonatal screening for metabolic diseases, whose biological samples were conserved in the DNA bank of the National Center for Medical Genetics. The molecular characterization of the genotypes was carried out using a PCR-ARMS. The GENEPOP 4.4 software and the statistical software package STATISTICA 8.0 were used for the analysis of genic and genotypic frequencies. Results: The population did not adjust to the Hardy-Weinberg equilibrium model for the gene evaluated. The estimated gene frequencies of VEGF +405 G> C polymorphism were 0.33 for the G allele and 0.67 for the C allele. The calculation of the genotypic frequencies resulted in 0.14, 0.37 and 0.49, for the variants GG, GC and CC, respectively. Conclusions: The allelic frequencies of VEGF.C were higher than the frequencies of the VEGF.G allele, being the VEGF GG the least represented genotype in the group studied(AU)

Impact of kras mutations in clinical features in colorectal cancer / Impacto das mutações kras e características clínicas em câncer colorretal

ABSTRACT Background: KRAS mutations are important events in colorectal carcinogenesis, as well as negative predictors of response to EGFR inhibitors treatment. Aim: To investigate the association of clinical-pathological features with KRAS mutations in colorectal cancer patients treated. Methods: Data from 69 patients with colorectal cancer either metastatic at diagnosis or later, were retrospectively analyzed. The direct sequencing and pyrosequencing techniques were related to KRAS exon 2. The mutation diagnosis and its type were determined. Results: KRAS mutation was identified in 43.4% of patients. The most common was c.35G>T (p.G12V), c.35G>A (p.G12D) and c.38G>A (p.G13D). No correlation was found between KRAS mutation and age (p=0.646) or gender (p=0.815). However, mutated group had higher CEA levels at admission (p=0.048) and codon 13 mutation was associated with involvement of more than one metastatic site in disease progression (p=0.029). Although there was no association between primary tumor site and mutation diagnosis (p=0.568), primary colon was associated with worse overall survival (p=0.009). Conclusion: The KRAS mutation was identified in almost half of patients. Mutated KRAS group had higher levels of CEA at admission and the mutation at codon 13 was associated with involvement of more than one metastatic site in the course of the disease. Colon disease was associated with the worst overall survival.

RESUMO Racional: Mutações KRAS são eventos importantes na carcinogênese colorretal como preditores negativos de resposta ao tratamento. Objetivo: Investigar a associação de características clinicopatológicas com mutações no KRAS em pacientes com câncer colorretal tratados. Métodos: Sessenta e nove pacientes com câncer colorretal metastáticos ao diagnóstico ou posteriormente foram analisados. As técnicas de sequenciamento direto e pirosequenciamento foram relacionadas ao éxon 2 do KRAS e o diagnóstico da mutação e seu tipo foram determinados. Resultados: A mutação KRAS foi identificada em 43,4% dos pacientes, c.35G>T (p.G12V), c.35G>A (p.G12D) e c.38G>A (p.G13D). Não foi encontrada correlação entre a mutação KRAS e a idade (p=0,646) ou o gênero (p=0,815). No entanto, o grupo mutado apresentou níveis mais altos de CEA na admissão (p=0,048). A mutação do códon 13 foi associada ao envolvimento de mais de um local metastático na progressão da doença (p=0,029); não houve associação entre o local primário do tumor e o diagnóstico de mutação (p=0,568); a doença primária do cólon foi associada com pior sobrevida global (p=0,009). Conclusão: A mutação KRAS foi identificada em quase metade dos pacientes. O grupo KRAS mutado apresentou níveis mais altos de CEA na admissão e a mutação no códon 13 foi associada ao envolvimento de mais de um local metastático no curso da doença. A doença do cólon foi associada com pior sobrevida global.

Allele and haplotype frequencies of human platelet and leukocyte antigens in platelet donors / Frequência alélica e haplotípica dos antígenos plaquetários e leucocitários humanos em doadores de plaquetas

ABSTRACT Objective To described the allele and haplotype frequencies of human leukocyte antigen genes at the -A, -B loci and human platelet antigen genes for human platelet antigen systems 1 to 9, 11 and 15 in blood. Methods We included 867 healthy unrelated volunteer donors who donated platelets between January 2011 and December 2014. Microarray genotyping was performed using a BeadChip microarray. Medium resolution typing of the human leukocyte antigen at loci A and B was carried out using sequence-specific oligonucleotide probe hybridization. We used multivariate analysis and our human leukocyte antigen population was compared to data from the United States national bone marrow donor program. Human platelet antigen results were compared to a literature review and data from around the world. Results Our human leukocyte antigen haplotype results were more similar to those of hispanics, followed by caucasians. Likewise, our human platelet antigen sample is more similar to those of Argentina, Rio Grande do Sul and Italy. Conclusion This was the first article that discusses human platelet antigen and human leukocyte antigen data together. Rare genotypes or antibody associations can make patient management difficult. A blood bank with genotyped donors allows for optimal transfusion and can contribute to better results. Our information can serve as basis for a database of platelet antigen polymorphisms.

RESUMO Objetivo Descrever as frequências alélicas e haplotípicas de genes dos antígenos leucocitários humanos nos loci -A,- B e dos antígenos plaquetários humanos para os sistemas HPA-1 a 9, 11 e 15. Métodos Foram incluídos 867 doadores voluntários, saudáveis, não relacionados, que doaram plaquetas por aférese entre janeiro de 2011 e dezembro de 2014. A genotipagem foi realizada usando microarray BeadChip. A tipificação de resolução intermediária dos antígenos leucocitários humanos loci A e B foi realizada por meio de hibridização com sonda para oligonucleotídeos por sequência específica. Utilizamos análises multivariadas e o antígeno leucocitário humano de nossa população foi comparado com a do programa nacional de doadores de medula óssea norte-americano. Já os resultados dos antígenos plaquetários humanos foram comparados à revisão da literatura e a dados de populações de outros países. Resultados Os resultados do haplótipo de antígenos leucocitários humanos são mais parecidos com os dos hispânicos, seguidos dos caucasianos. Igualmente, a amostra de antígenos plaquetários humanos foi mais semelhante às da Argentina, do Rio Grande do Sul e da Itália. Conclusão Este foi o primeiro artigo a discutir antígenos plaquetários e leucocitários humanos simultaneamente. Genótipos raros ou associações de anticorpos podem dificultar o manejo clínico do paciente. Um banco de sangue com doadores genotipados permite um melhor resultado e transfusão possíveis. Estas informações podem servir de base para um banco de dados sobre polimorfismos de antígenos plaquetários.

Distribution of adeG, adeB, adeE, adeY, abeM, and adeJ Efflux Pump Genes in Clinical Isolates of Acinetobacter Species from Korea

BACKGROUND: The aim of the present study was to determine the frequency of six efflux pump genes in Acinetobacter clinical isolates collected from South Korean hospitals. METHODS: In this study, we used a total of 339 Acinetobacter strains, comprising 279 Acinetobacter calcoaceticus–Acinetobacter baumannii (ACB) complex and 60 non-ACB complex strains. We performed specific PCR assays to detect adeG, adeB, adeE, adeY, abeM, and adeJ, transporter genes of the multidrug efflux pumps AdeFGH, AdeABC, AdeDE, AdeXYZ, AbeM, and AdeIJK, respectively. RESULTS: Frequencies of six efflux pump genes varied according to the species of Acinetobacter. Frequencies of adeE, abeM, and adeJ between A. baumannii group and A. nosocomialis group were found to be significantly different. Significant differences were found in the frequencies of adeB, adeE, adeY, and adeJ among the susceptible A. baumannii (SAB), multidrug-resistant A. baumannii (MDRAB), and extensively drug-resistant A. baumannii (XDRAB) groups within the 154 strains of A. baumannii. The frequencies of efflux pump genes in imipenem-susceptible and imipenem-nonsusceptible groups were significantly different for adeB, adeY, and adeJ. The frequencies of efflux pump genes in ciprofloxacin-susceptible and ciprofloxacin-nonsusceptible groups were significantly different for adeB and adeY. No significant difference was found in the frequency of efflux pump genes among groups sampled from different regions of Korea, across 86 strains of A. baumannii collected in 2012. CONCLUSIONS: The frequencies of six efflux pump genes obtained in this study demonstrate the fundamental epidemiological feature of efflux pump genes in Korean Acinetobacter clinical isolates.

Relationship between phosphodiesterase 4D gene rs966221 single nucleotide polymorphisms and ischemic stroke / 中华老年心脑血管病杂志

Objective To study the relationship between phosphodiesterase 4D (PDE4D) gene rs966221 single nucleotide polymorphisms (SNPs) and ischemic stroke (IS) in Guangxi Zhuang population.Methods One hundred and one IS patients from Guangxi Zhuang Autonomous Region served as IS pgroup and 104 healthy subjects undergoing physical ecamination served as control group in this study.Their PDE4D gene rs966221 SNPs were detected by SNaPshot technique.The genotypes and frequencies of alleles were compared between the two groups and the relationship between PDE4D gene rs966221 SNPs and IS was analyzed.Results No significant difference was found in the GG,GA,AA genotypes and in the frequencies of G and A alleles between the two groups (0.99％ vs 3.85％,29.70％ vs 21.15％,69.31％ vs 75.00％,P＞0.05;15.84％ vs 14.42％,84.16％ vs 85.58％,P＞0.05).Univariate and multivariate logistic regression analysis showed that the PDE4D gene rs966221 SNPs were not related with the risk of IS in dominant AA vs GG+GA,recessive GG vs AA+GA and additive GG vs AA genetic models (P＞0.05).Conclusion The PDE4D gene rs966221 SNPs are not related with IS in Guangxi Zhuang population.

Association between single nucleotide polymorphism of SEPT14 gene and sporadic PD / 中华老年心脑血管病杂志

Objective To study the association between the single nucleotide polymorphism (SNP) of SEPT14 (rs77231105,rs10241628,rs11981883,rs73701167) and sporadic PD in Chinese Han populationin of Southwest Shandong.Methods One hundred and eighty PD patients from Southwest Shandong served as PD patient group and 200 healthy subjects from Southwest Shandong served as control group in this study.The distribution frequencies of alleles and genotypes in SNP of rs77231105,rs10241628,rs11981883 and rs73701167 were compared by PCR and sequencing respectively.Results No significant difference was found in the distribution frequencies of alleles and genotypes in rs77231105,rs10241628,rs11981883 between the two groups (P＞0.05).The distribution frequency of rs73701167 was significantly higher in PD patient group than in control group (31.1％ vs 20.5％,OR=1.75,95％CI=1.261-2.428,P=0.001).Conclusion The SNP of SEPT14 rs77231105,rs10241628 and rs1198188 are not associated with PD,the SNP of rs73701167 is associated with PD in Chinese Han population of Southwest Shandong.The allele C is a risk factor for PD.

Association of NLRP3 gene polymorphism with hypertension and carotid atherosclerosis in patients of Xinjiang Kazakh nationality / 中华老年心脑血管病杂志

Objective To study the association of NLRP3 gene polymorphism with primary hyper tension (PH) and carotid atherosclerosis (CA) in patients of Xinjiang Kazakh nationality.Methods Three hundred and fifty PH patients of Xinjiang Kazakh nationality were divided into CA group (n=150) and CA-free group (n=200) with 200 Xinjiang Kazakh nationality people undergoing physical examination served as a control group in this study.Their NLRP3 rs10754558 genotypes and alleles were detected using the Tapman probe method and their serum IL-1β level was measured by ELISA.Results The detection rate of rs10754558 genotypes and alleles was significantly higher in CA group than in control group (20.0％ vs 9.0％,43.0％ vs 34.8％,P＜0.05).No significant difference was found in NLRP3 gene types and G alleles between the two groups (P＞ 0.05).The serum IL-1β level was significantly higher in CA and CA-free groups than in control group (2.79±0.83 ng/L and 2.82±0.92 ng/L vs 2.21±0.91 ng/L,P＜0.05) and in GG gene type carriers of CA and CA-free groups than in those of control group (3.40±± 0.37 ng/L and 3.35±0.43 ng/L vs 2.21±0.90 ng/L,P＜0.05).Conclusion NLRP3 rs10754558 gene polymorphism is associated with genetic susceptibility to hypertension and carotid atherosclerosis in patients of Xinjiang Kazakh nationality.

The prevalence and genetic characterization of 22750 cases of beta-thalassemia in Fujian Province / 中华检验医学杂志

Objective To analyze the molecular characterization and prevalence of beta-thalassemia in Fujian Province .Methods RDBwas applied to identify 17 point mutations of beta gene and 3 point mutations of alpha gene .Gap-PCRwas applied to identify 3 deletions of alpha gene , MLPA and DNA sequecing were applied to identify the rare mutational genotype of beta-thalassemia.Results 3515 cases (15.45％)ofβ-thalassemia were confirmed.15 genotypes were found in the studied subjects .βIVS-2-654(C→T)/βN, βCD41-42(-TCTT)/βN, βCD17(A→T)/βN, β-28(A→G)/βN, βCD27-28( +C)/βN, and βCD26(G→A)/βN were the mostcommon genotypes in Fujian Province , accounting for 41.76％, 30.50％, 12.46％, 5.46％, 2.93％and 1.82％respectively , It was found that the total frequency of them was 94.93％in our study.13 cases of deletional β-thalassemia were detected , including 6 cases of Southeast Asia subtype ( SEA-HPFH) , 6 cases of Chinese subtype Gγ(Aγδβ)0 and 1 case of 1.35kb deletion(NG-000007.3:g.69997-71353 del 1357) in one subject .13 cases of rareβ-thalassemia were detected , including Hb J-Bankok in 8 subjects and Hb New York in 5 subjects were diagnosed .Conclusions As a high-risk area forβ-thalassaemia, the detection of deletional β-thalassemia and rare β-thalassaemia subtypes should be screened in addition to the common β-thalassemia genes , so as to demonstrate the results of β-thalassemia gene detection in this region .Those screening results are useful for genetic counseling and can effectively reduce the birth of children with moderate to severe β-thalassaemia .

Polymorphism of the cox-2 gene and susceptibility to colon and rectal cancer / Polimorfismo do gene cox-2 e a suscetibilidade ao câncer de cólon e reto

ABSTRACT Background: The colorectal neoplasm is the fourth most common malignancy among males and the third among females. In the Western world is estimated that 5% of the population will develop it, making this disease a major public health problem. Aim: To analyze the prevalence of the polymorphism -765G / C region of the COX-2 gene in colorectal cancer patients compared to a control group, analyzing the possible association between this polymorphism and susceptibility to colorectal cancer. Method: This is a case-control study with 85 participants. Were selected 25 with colorectal cancer (case group) and 60 participants without colorectal neoplasia (control group). The molecular genetic analysis was perform to identify the polymorphism -765G / C COX2 gene with standard literature technique. In addition, patient's clinical and pathological data were analyzed. Results: There was a light increase in prevalence between men in the case group, although this difference was not statistically significant. The results showed a high prevalence of GC and CC genotype in individuals with colorectal cancer, demonstrating an association between the presence of the polymorphism in the COX2 gene and susceptibility to colorectal cancer in this pattern (p=0.02). Similarly, there was also difference in allele frequencies in the groups. When patients with cancer were separated by tumor location, there was a higher prevalence of polymorphism in the left colon (p=0.02). Conclusion: The polymorphism in the COX2 gene is associated with increased susceptibility to colorectal cancer, specially rectosigmoid tumors.

RESUMO Racional: A neoplasia colorretal representa a quarta malignidade mais comum entre homens e a terceira entre as mulheres. No mundo ocidental estima-se que 5% da população a desenvolverá, tornando-a grave problema de saúde pública. Objetivo: Analisar a prevalência de polimorfismo na região -765G/C do gene COX-2 em pacientes com câncer colorretal em relação a um grupo controle, analisando a possível associação entre este polimorfismo e a suscetibilidade a ele. Método: Foram incluídos neste estudo caso-controle 85 participantes. Selecionou-se 25 com neoplasia colorretal (grupo caso) e 60 pacientes sem neoplasia colorretal (grupo controle). Realizou-se análise genético-molecular para identificação do polimorfismo -765G/C do gene COX2 com técnica padrão da literatura. Além disso, foram levantados dados clínicos e anatomopatológicos dos pacientes. Resultado: Constatou-se discreto aumento de prevalência entre os homens no grupo caso, embora esta diferença não fosse estatisticamente significante. Os resultados revelaram alta prevalência do genótipo GC e CC nos indivíduos com câncer colorretal, demonstrando associação entre a presença do polimorfismo no gene COX2 e a suscetibilidade ao câncer colorretal nesta amostra (p=0,02). Similarmente, também se observou diferença nas frequências alélicas em relação aos grupos. Quando os pacientes com a neoplasia foram separados por localização do tumor, verificou-se maior prevalência do polimorfismo em pacientes de cólon esquerdo (p=0,02). Conclusão: O polimorfismo no gene COX2 está associado com a maior suscetibilidade ao câncer colorretal, especialmente em tumores do retossigmoide.

Associations of single nucleotide polymorphisms of UCP genes with diabetic retinopathy in Chinese Han population / 中华实验眼科杂志

Background Researches showed that elevatory blood glucose level results in long-term damage of cells and tissue,or metabolic memory phenomenon,and manipulation of hyperglycemic memory is a good approach in the prevention of diabetic complications.However,its mechanism is not clear.It is speculated that the pathogenesis of diabetic retinopathy (DR) in diabetic patients may be associated to related mechanisms.Uncoupling proteins (UCPs) can decrease the production of reactive oxygen species (ROS),which may be related to DR.Objective This study was to explore the association between DR and the single nucleotide polymorphisms (SNPs) of UCP genes in Chinese Han population with type 2 diabetes.Methods A cross-sectional study was performed.This study was approved by Ethic Committee of Affiliated First Hospital of Shanghai Jiao Tong University and complied with Declaration of Helsinki,and written informed consent was obtained from each subject prior to any medical examination.One thousand eight hundreds and seventy-five patients with type 2 diabetes mellitus were enrolled in Xinjing district of Shanghai city by cluster sampling from November 2014 to January 2015.The demographic and medical baseline characteristics,ocular examination and laboratory tests were obtained and periphery blood of 2 ml was collected for extraction of DNA.Eight tag SNPs of UCP1,three tag SNPs of UCP2,and seven tag SNPs of UCP3 were selected as marker locus for the detection of genotype by Sequenom Mass ARRAY.Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry platform were used for genotyping.Hardy-Weinberg equilibrium (HWE) analysis,allele and genotype frequencies,haplotype analysis,and association tests for DR and SNPs were performed by SAS and SHEsis software.Results A total of 530 DR patients were checked out from 1 875 subjects with type 2 diabetes mellitus,with the detection rate of 28.27％.rs660339 locn of UCP2 gene and rs1626521,rs668514 locus of UCP3 gene appeared to have low detectable rates,and the secondary allele base frequency of rs632862 in UCP2 gene was ＜0.01 and rs15763 of UCP3 gene was unmatched with HWE,therefore,these locus analysis was not included.In 13 SNPs locus included in the analysis,only 2 SNPs of UCP1 gene were related to DR.Compared with the non-diabetic retinopathy (NDR) patients,the G allele frequency of rs10011540 was increased (P =0.03,OR =1.31,95 ％ confidence interval[CI] =1.03-1.67,and T allele frequency of rs3811787 was decreased (P=0.04,OR=0.86,95％ CI=0.75-0.99) in DR patients.Genotyping detection showed that the C/C and A/A frequencies of rs3811790 in UCP1 gene were significantly more and C/A frequency was less in DR patients than those in NDR patients (all at P＜0.01).The logistic regression analysis indicated an association of SNPs of rs10011540 and rs3811787 with DR independent from glucose and disease duration.Conclusions The SNPs of rs10011540 and rs3811787 locus in UCP1 gene are associated with DR in Chinese type 2 diabetes patients.

Relationship of methylene tetrahydrofolate reductase gene polymorphism and homocysteine with coronary heart disease in females / 中国基层医药

Objective To explore the relationship between methylene tetrahydrofolate reductase (MTHFR) gene polymorphism and homocysteine (Hcy),and further to investigate their correlation to coronary heart disease (CHD) in females.Methods This study involved 29 premenopausal women with CHD,57 postmenopausal women with CHD,50 men with CHD and 46 postmenopausal women with non-CHD.All patients underwent coronary angiography.The patients' gender,age,history of hypertension,diabetes and smoking were recorded.The plasma Hcy level,blood lipids and MTHFR gene polymorphism were examined.Results The level of Hcy in postmenopausal women with CHD was (18.11±7.21)μmol/L,which was significantly higher than (15.01±6.53)μmol/L in premenopausal women with CHD,(12.98±5.46)μmol/L in postmenopausal women with non-CHD group and (14.32±6.01)μmol/L in men with CHD group (t=5.23,3.65,5.08,all P<0.05).The frequency of the MTHFR TT genotype in postmenopausal women with CHD was 28.1% which was significantly higher than postmenopausal women with non-CHD(17.4%)(χ2=5.13,P<0.05),but there was no statistically significant difference with the other two groups.The plasma Hcy level in patients with TT genotype was significantly higher than that with CT or CC genotype in all groups.Multivariate logistic regression analysis showed a significant positive correlation in Hcy and TT genotype.Multivariate logistic regression analysis showed that smoking,Hcy,hypertension and diabetes were independent risk factors for CHD.The odds ratios(OR) of Hcy for CHD was 2.601 (95% confidence interval,1.326 to 5.745).Conclusion Hcy may be an independent risk factor for CHD in females.MTHFR C677T genotype is significantly associated with hyperhomocysteinemia,and its mutation frequency increases significantly in patients with CHD,but MTHFR mutation is not related with the incidence of CHD.

Preliminary analysis on antigen polymorphism of HLA-B15 and HLA-B40 groups among Han population in Guangxi area / 国际检验医学杂志

Objective To investigate the allele and specificity distribution situation of HLA-B15 group and HLA-B40 group antigens among Han population in Guangxi area and to explore their possible influence on transplantation donors selection in clinic.Methods The blood samples of 1 644 Han donors in Guangxi region were performed the HLA-B genotyping by PCR-SBT,the frequencies of each allele were calculated by the direct computing method.The antigen specificity of various alleles were analyzed,then the gene frequencies of HLA-B15 and HLA-B40 groups were compared with those from other populations.Results The gene frequency at HLA-B locus in 1 644 Han persons was inconsistent with the Hardy-Weinberg equilibrium(P<0.05).Fourteen alleles in HLA-B15 group were detected out,which belonged to 5 kinds of antigen specificity.In the HLA-B40 group,6 alleles were detected out,which belonged to two kinds of antigen specificity.Conclusion The antigen polymorphism of HLA-B15 and HLA-B40 groups among Han population in Guangxi area is close to that in southern Chinese Han populations,but which still keeps its characteristics of Guangxi area.

Survey and study on FYES and FYX alleles of Duffy blood group in Nanjing Han population / 国际检验医学杂志

Objective To investigate the FYES and FYX allele expression situation of Duffy blood group in Han population of Nanjing area.Methods The genomic DNA was randomly extracted from peripheral EDTA-K2 anticoagulation blood samples in 200 voluntary blood donors and Duffy blood group FYA and FYB allele typing was performed by PCR-SSP.The EYES and FYX allele sequence charateristics of Duffy blood group were analyzed by adopting Sanger double deoxygenation gene sequencing method.Results The PCR genotyping results were consistent with the sequencing results.Among 200 samples,180 cases were FYA/FYA and 20 cases were FYA/FYB;the sequencing results showed that FYES and FYX allele expression was not been found in 200 samples.Conclusion The expression frequencies of FYES and FYX alleles are extremely low in Han population of Nanjing area,which has significant difference compared with other races.

Analysis of online Mendelian inheritance in man / 中国生化药物杂志

Objective To analyze the data from Online Mendelian Inheritance in Man (OMIM) to understand more about it, and provide reference to researchers using this database.Methods 19414 mutations which have definite relevant phenotypes from OMIM were obtained, then these mutations with three databases (1000 Genome Project,GO-ESP,ExAC) which record the mutation frequency in different population were compared.Results Most of the phenotype-related mutations from OMIM are rare mutations whose mutation frequency is less than 1%:18866 in 1000 Genome Project, 18981 in GO-ESP, 18979 in ExAC.The number of mutation whose frequency is more than 1% is 548433435 in 1000 Genome Project, GO-ESP, ExAC, respectively.And there are 320 mutations whose frequency is more than 1% in all databases.In all phenotypes, there are 127 polymorphism phenotypes, 584 susceptibility phenotypes, while in 320 ( 1.6%) phenotypes with common mutations, there are 62 polymorphism phenotypes, 88 susceptibility phenotypes and occupies 48.8%, 15.1%, respectively.Conclusion Approximately 97.5% mutations in OMIM are rare mutations.Polymorphism and susceptibility enrich in common mutations, especially in the mutation whose frequency is more than 10%.

Study on haptoglobin polymorphism and plasma concentration in patients with polycystic ovarian syndrome / 上海交通大学学报（医学版）

Objective·To investigate the correlation between the serum haptoglobin (Hp) level and the metabolic parameters in patients with polycystic ovarian syndrome (PCOS), and explore the distribution of Hp genotype and allele frequency in PCOS patients and their correlations with PCOS. Methods·A total of 106 patients with PCOS and 86 cases of patients with non-hyperandrogenic and regular menstruation (control group) were enrolled. Serum Hp level was measured by enzyme-linked immunosorbent assay (ELISA); Hp genotype and allele frequency were determined by polymerase chain reaction (PCR), respectively. Results·The serum Hp level in PCOS group was significant higher than that in the control group (P=0.000). Correlation analysis reveals that serum Hp level was positively related to body mass index (BMI) (P=0.000) and homeostatic model assessment insulin resistance (HOMA-IR) (P=0.000). Compared with control group, proportion of Hp2-2 genotype (Hp2/Hp2) increased significantly in PCOS group (P=0.006), and the frequency of Hp2 allele was also higher (P=0.002). Conclusion·Serum Hp level was positively related to BMI and HOMA-IR, which maybe associated with the occurrence and development of obesity and insulin resistance. Patients with Hp2-2 genotype might have genetic predisposition to PCOS, and high frequency Hp2 allele was found in them.

The characteristic of gene polymorphism of Kell blood group in Zhuang population from Guangxi region in China / 重庆医学

Objective To investigate gene polymorphism of Kell blood group in different Zhuang population from Guangxi region .Methods The genotypes of Kell blood group of 1025 non‐related individuals in different areas of Guangxi Zhuang popula‐tion were analyzed by PCR‐SSP .Results The Kell antigen in all individuals was homozygous ,the gene frequency of K and Jsa was 0 ,while that of k and Jsb was 1 .000 .Conclusion The distribution characteristic of Kell blood group in Guangxi Zhuang population was monomorphism ,which was similar to other Chinese population reported by literatures .