9p21 Locus Polymorphisms: Risk and Severity Factors of Coronary Artery Disease in Venezuelan Patients

Abstract Background: The 9p21 region is the most relevant locus associated with coronary heart disease in different populations. However, there are no studies that prove that this region is a risk factor in the Venezuelan population. Objectives: To analyze whether or not the 9p21 rs1333049 polymorphism is a risk factor for acute myocardial infarction (AMI) in Venezuelan patients, as well as to investigate its correlation with cardiovascular risk factors (CVRF), age of occurrence, type and severity of infarction, and the correlation of the rs10757274 polymorphism with severity of coronary artery disease. Methods: This was an association study, including 487 unrelated Venezuelan individuals, grouped in 354 patients with AMI and 133 controls. The rs1333049 and rs10757274 polymorphisms were determined using the polymerase chain reaction (PCR) technique with sequence-specific primers. The analysis of association was determined using the SNPStats tool. The continuous variable description and the correlations were performed using the SPSS statistical software. Significance was established at p<0.05. Results: A positive correlation was observed between the rs1333049 polymorphism and the presence of hypertension ( r: 0.145, p: 0.006), and between hypertension and heart infarction ( r: 0.318, p: <0.0001). A positive correlation was found between the rs10757274 polymorphism and the number of coronary vessels that presented obstructive lesions in patients aged ≤ 55 years ( r: 0.276, p: 0.0078). Conclusion: The rs1333049 polymorphism at the 9p21 locus is correlated with hypertension in Venezuelan patients, while the rs10757274 polymorphism is associated with the progression of coronary atherosclerosis, suggested by the correlation with the number of coronary vessels that presented significant obstructive lesions.

Research Progress on the Relationship between Genetic Polymorphism and Violent Behavior of Patients with Schizophrenia / 法医学杂志

Schizophrenia is a common disease characterized by thinking obstructions and accompanied by cognitive, emotional and behavioral disorders. Under the control of psychiatric symptoms, patients with schizophrenia may self-injure or impulsively wound others, resulting in public risk and increase in the burden of family and society. In recent years, many studies have shown that the violent behavior of patients with schizophrenia is related to genetic factors. This article reviews the research progress on the relationship between genetic polymorphism and violent behavior of patients with schizophrenia, analyzes the possible mechanism of the correlation between the two, puts forward the limitations of current research and the directions of future research, and provides scientific basis for risk assessment and prevention of violent behavior of patients with schizophrenia.

Polymorphisms of 19 STR Loci in Guizhou Han Population and Their Forensic Application / 法医学杂志

Objective To investigate the allelic distribution of 19 autosomal STR loci in Guizhou Han population,and to estimate the forensic application value.Methods The 19 autosomal STR loci in 520 unrelated healthy individuals from Guizhou Han population were studied using GoldeneyeTM 20A kit.The 310 genetic analyzer was used for capillary electrophoresis,and the GeneMapper(R) ID v3.1 for genotyping.Results The heterozygosis,the discrimination power,the probability of exclusion,the polymorphism information content,the cumulative discrimination power and the cumulative probability of exclusion of the 19 STR loci were 0.603 8-0.9164,0.7900-0.985 6,0.295 5-0.8269,0.553 5-0.9089,1-1.2300×10-22 and 0.999 999 99,respectively.Compared with other five Han populations in pairwise allelic frequencies,Guizhou Han only had significant differences with Shandong Han,Liaoning Han and Shanxi Han.Conclusion The 19 autosomal STR loci such as D19S433 have a highly genetic polymorphic in Guizhou Han population,which have application values in the researches of population genetics and forensic genetics.

Meta analysis of the association between vascular endothelial growth factor-2578C/A polymorphism and risk for diabetic retinopathy / 中华实验眼科杂志

Background Studies showed that vascular endothelial growth factor (VEGF) plays an important role in the development and progress of diabetic retinopathy (DR),and the association between VEGF-2578C/A polymorphism(SNPs) and risk for DR is a hotspot.Objective This Meta analysis aimed to investigate the comprehensive and reliable conclusion in the association of VEGF-2578C/A SNPs and risk for DR in different races.Methods A systematic search of electronic databases including PubMed,Cochrane Library,EMbase,VIP,Wanfang technological,CNKI and reference lists of relevant articles was carried out until April,2014.Case-control studies on the relationship between VEGF-2578C/A SNPs and DR were selected based on inclusion and exclusion criteria,and the relevance of VEGF-2578C allele to DR,the relevance of VEGF-2578C/A SNPs to DR and the relevance of VEGF-2578A allele to Caucasian DR were quantitatively analyzed.Begger funnel plot of publication biases on the relationships of VEGF SNPs with the risk of DR under the allele and dominant models was drown.RevMan 5.0 software was used for the statistical analysis.The pooled odds ratio (OR) and corresponding 95％ confidence interval (CI) were used to assess the strength of the association.Results A total of 1 228 DR cases and 1 224 diabetes controls without retinopathy(DWR) were included from 8 independent studies (9 groups of data).A significant relationships between VEGF-2578A allelic gene and VEGF-2578AA gene type with DR were found in all samples,and the A allelic gene and AA gene type were the risk genes of DR (A versus C:OR=1.39,95％ CI=1.08-1.80,Z=2.52,P=0.01;AA versus CC+C/A:OR=1.53,95％ CI=1.05-2.24,Z=2.20,P=0.03;CC versus AA+C/A:OR=0.70,95％ CI=0.50-0.98,Z =2.10,P =0.04).When the other two studies which did not meet the HardyWeinberg Equilibrium were incorporated in a sensitivity analysis,the results were not materially altered.VEGF-2578 A allelic gene was the risk gene to Europeans with DR (OR =1.50,95％ CI=1.02-2.21,Z =2.07,P =0.04),but not among Asians in subgroup analysis (P＞0.05).No significant publication bias was found.Conclusions The Meta analysis demonstrates that VEGF-2578C/A is associated with DR in Europeans but not in Asians.Further case-control studies based on larger sample size are still needed,especially in Asians.

The correlation analysis of interleukin-1 family genotypes with coronary heart disease in elderly patients / 中华老年医学杂志

Objective To investigate the correlation of interleukin-1 family genotypes,including interleukin-1 (IL-1α,IL-1β) and interleukin-1 receptor antagonist (IL-1Ra),with coronary heart disease (CHD) and serum lipoprotein level in the elderly.Methods Interleukin-1 family genotypes were detected in 318 elderly controls and 329 elderly CHD patients by polymerase chain reaction and restriction fragment length polymorphisms method.Serum levels of lipoproteins were inspected simultaneously.Results The TT and Ⅰ / Ⅰ or Ⅰ/Ⅳ genotype frequency of IL-1Ra was 90.3％ in elderly CHD patients,but 82.4％ in controls.Carriers with TT,Ⅰ / Ⅰ or Ⅰ/Ⅳ genotype of IL-1Ra were at an increased risk with an odds ratio of 1.98 in elderly CHD patients as compared with controls (x2=8.55,95％ CI:1.25-3.16).The TT and Ⅰ/Ⅰ or Ⅰ/Ⅳ genotype frequency of IL-1Ra was 96.2％ in elderly CHD patients with acute coronary syndrome,but 84.8％ in elderly CHD patients with stable angina.Carriers with TT,Ⅰ / Ⅰ or Ⅰ/Ⅳ genotype of IL-1Ra were at an increased risk with an odds ratio of 4.54 in acute coronary syndrome group as compared with stable angina group (x2=12.17,95％CI:1.81-11.36).The CT or TT genotype frequency of IL-1α-889 was 22.8％ in acute coronary syndrome group,but 7.6 ％ in stable angina group.Carriers with CT or TT genotype of IL-1α-889 were at an increased risk with an odds ratio of 3.59 as compared with stable angina group (x2 =14.93,95％CI:1.82-7.03).There were no significant differences in levels of serum lipoproteins among the different genotypes (P＞0.05).Conclusions In elderly patients with coronary heart disease,IL-1α(-889) CT or TT genotype carriers are at high risk for acute coronary syndrome,but IL-1Ra CC,TC,Ⅰ / Ⅱ or Ⅱ / Ⅱ genotype carriers are at a low risk for CHD or severe CHD.

Correlation between polymorphism of cytochrome P450 1A2 gene and antidepressant clinical efficacy of duloxetine / 中华行为医学与脑科学杂志

Objective To investigate the relationship between C734A and G-2964A polymorphism of cytochrome P450 1A2 gene and clinical efficacy of duloxetine.Methods 223 patients with depression were treated with duloxetine for six weeks.The clinical efficacy was evaluated with the Hamilton rating scale for depression (HAMD) ;single nucleotide polymorphism (SNP) at position C734A and G-2964A of CYP1A2 gene were identified with restriction fragment length polymorphism(RFLPs) ;then one-way ANOVA was adopted to analyze the relationship between SNP and clinical efficacy.Results (1) In 223 patients,the frequency of allele A at locus 734 was 63.64％,while that of allele A at locus-2964 was 26.82％.(2) 220 patient underwent the whole treating course.The conjoint analysis of two locuses indicated that the decreasing ratio of HAMD score of high-activity group,middle-activity group and low-activity after treatment was (56.05± 10.13) ％,(66.36± 8.66) ％ and (73.82± 7.10) ％ respectively,the differences obtained by pairwise comparison of the three groups were of statistical significance(P＜0.01).Conclusion There is close relationship between C734A and G-2964A polymorphism of CYP1A2 gene and clinical efficacy of duloxetine in the treatment for depression.

Densidade mamográfica e polimorfismo do gene do receptor estrogênico em mulheres após a menopausa / Mammographic density and polymorphism of the estrogen receptor gene in women after menopause

Introdução: Receptores hormonais modulam a resposta dos tecidos ao estímulo humoral. Evidências epidemiológicas mostram que as variações dos genes que regulam a biossíntese e metabolização dos receptores estrogênicos (RE) causam alterações no efeito dos estrógenos no tecido mamário, podendo explicar as variações individuais da densidade mamográfica. A alta densidade mamográfica é um fator de risco importante para o câncer de mama.Objetivo: Avaliar a associação das características clínicas e dos polimorfismos do gene do REalfa (XBal, Pvull e (GT)n) com a densidade mamográfica em mulheres após a menopausa. Casuística e métodos: Avaliaram-se prospectivamente 463 mulheres após a menopausa, sendo que 308 mulheres com mamas densas e 155 com mamas não densas, segundo os critérios do ACR-BIRADS (2003) por avaliação objetiva computadorizada, com idade de 45 a 60 anos, não usuárias de terapia hormonal nos últimos 12 meses e sem antecedentes pessoais de câncer de mama. Amostras de sangue periférico foram obtidas para extração de DNA e análise dos polimorfismos presente no íntron 1 e região promotora (Xbal, Pvull e (GT)n) do gene do RE?. Resutados: Dos fatores considerados de risco para o câncer de mama, houve associação com a densidade mamográfica: idade (p=0,005); medida da cintura abdominal (p=0,001); número de gravidezes (p=0,007); idade ao ter o 1º filho (p=0,035); antecedentes familiares (p=0,035); tempo decorrido deste a data da última menstruação (p=0,007) e índice de massa corpórea (p=0,022). Foi verificada diferença significante entre os grupos de mama densa e não densa para distribuição do genótipo do polimorfismo Pvull (p=0,024). Xbal (p=0,362) e, para o polimorfismo de repetição (GT)n (p=0,151) a associação não foi significante. Conclusão: Apenas o polimorfismo Pvull e os fatores clínicos: idade, cintura abdominal, número de gravidezes, idade ao ter o primeiro filho, antecedentes familiares de câncer de mama, tempo decorrido desde a data da...

Introduction: The hormone receptors modulate the tissue response to hormonal stimulation. Epidemiological evidences show that the variations in genes that regulate the biosynthesis and metabolism of estrogen receptors (ER) cause changes in the effect of estrogen in breast tissue, which may explain individual variations of the mammographic density. High mammographic density is an important risk factor for the breast cancer. Objective: Evaluating the association of clinical characteristics and polymorphisms of the gene ERalfa [XbaI, PvuII and (GT)n] and mammographic density in postmenopausal women. Methods: It was prospectively evaluated 463 postmenopausal women - 308 women with high mammographic density (HMD) and 155 controls (to 50% density or less), according to the criteria of the ACR - BIRADS (2003 ) computed objective assessment , aged 45 to 60 , nonusers of hormone therapy in the past 12 months and with no personal history of breast cancer. Peripheral blood samples were obtained for DNA extraction and analysis of this polymorphism in intron 1 and promoter [XbaI, PvuII and (GT) n)] of the ERalfa gene region. Results: Among the risk factors for breast cancer there was an association with mammographic density: age (p = 0.005), waist circumference (p = 0.001), number of pregnancies (p = 0.007), age of first birth ( p = 0.035 ), family history (p = 0.035), time after menopause (p = 0.007 ) and body mass index (p = 0.022). Significant difference was observed between the groups of HMD and control only for the distribution of the polymorphism PvuII (p = 0.024 ). XbaI (p = 0.362 ) and for repeat polymorphism (GT) n (p = 0.151) the association was not significant. Conclusion: Only the PvuII polymorphism and clinical factors: age, waist circumference, number of pregnancies, age of first birth, family history of breast cancer, time after menopause and body mass index proved to be associated with high mammographic density after menopause.

Genetic diversity of phospholipase C-encoding genes among 102 clinical isolates of Mycobacterium tuberculosis / 中华传染病杂志

Objective To explore and analyze genetic mutations of phospholipase C (PLC)-encoding genes plcABCD among clinical isolates of Mycobacterium tuberculosis and to provide scientific basis for understanding virulence and pathogenesis of Mycobacterium tuberculosis. Methods A total of 102 isolates from patients with active tuberculosis were identified. Bacterial DNA was extracted. All plcABCD genes were amplified by polymerase chain reaction (PCR) and checked for deletions or mutations by agarose gel electrophoresis. Results According to presence or absence of plcABCD genes, 102 isolates were divided into 13 genotypes. Thirty-one (30.39%) isolates were plc wild genotype with all plcABCD genes; 71(69. 61%) isolates were plc mutant type with different plc gene deletions. Of 71 plc mutant isolates, 48 missed only one of four plc genes, 14 had deletions of 2 plc genes, 8 were triple mutants and 1 was quadruple mutant. There were 61 (59. 80%) isolates with plcD gene mutation, while the mutation rates of plcA, plcB and plcC genes were lower, which were 15. 69%(16/102), 9. 80%(10/102) and 16. 67%(17/ 102), respectively. Conclusion This study shows great diversity in plcABCD genes among clinical isolates of Mycobacterium tuberculosis, with the most common of plcD.

Association between the 936C/T polymorphism in the 3'-untranslated region of vascular endothelial growth factor gene and diabetic peripheral neuropathy in China / 中华内分泌代谢杂志

Objective To elucidate the relationship between a 936C/T mutation at 3'-untranslated region of human vascular endothelial growth factor(VEGF) gene and diabetic peripheral neuropathy ( DPN ). Methods All subjects recruited in this study were assigned into DM (n = 92, diabetes without neuropathy, retinopathy or nephropathy), DPN (n = 102, diabetes with peripheral neuropathy only ), and healthy control (n = 120 ) groups,respectively. The gene polymorphism was determined by PCR-RFLP, as well as the other clinical parameters including serum VEGF by ELISA. Results The frequencies of both genotype CC and allele C were significantly higher in DPN group than those in either DM group(x2 = 5.578 and 5.614, P＜0. 05 ) or control group (x2 = 9. 406 and 9. 677, P＜0. 05 ). However, the frequencies of genotype(CT+TT) and allele T were significantly lower in DPN group than that in either DM group(x2 =5.578 and 5.614, P＜0. 05) and control group (x2=9.406 and 9.677, P＜0.05). The multivariate logistic regression analysis showed that the levels of HbA1c, total cholesterol, low-density lipoproteincholesterol( LDL-C ), and serum VEGF positively correlated with DPN, while the 936C/T polymorphism of VEGF gene negatively correlated with DPN(β= -1. 046, OR=0. 457, P=0. 006, 95% CI: 0. 166-0. 741 ). Conclusions Allele 936C of VEGF gene may serve as a genetic marker susceptible to DPN, while allele 936T may be a protective genetic marker of DPN.

Diferenciación genética de tres poblaciones colombianas de Triatoma dimidiata (Latreille, 1811) mediante análisis molecular del gen mitocondrial ND4 / Genetic differentiation of three Colombian populations of Triatoma dimidiata (Heteroptera: Reduviidae) by ND4 mitochondrial gene molecular analysis

Introducción. Triatoma dimidiata es el segundo vector más importante de la enfermedad de Chagas en Colombia, después de Rhodnius prolixus. El conocimiento de la composición genética y la diferenciación de poblaciones es fundamental para el adecuado diseño e implementación de estrategias de control y vigilancia vectorial. Objetivo. Determinar el nivel de variabilidad y diferenciación genética en tres poblaciones colombianas de T. dimidiata provenientes de distintas localidades y hábitats, mediante el análisis molecular de un fragmento del gen mitocondrial ND4. Materiales y métodos. Se analizó el nivel de polimorfismo y la estructura genética de dos poblaciones silvestres de los departamentos de La Guajira (n=10) y Santander (n=10), y de una población intradomiciliaria (n=15) y peridomiciliaria (n=5) del Cesar. Para tal fin, se analizaron las secuencias de nucleótidos de un fragmento del gen mitocondrial ND4. Resultados. T. dimidiata en Colombia demostró tener gran diversidad genética, tanto a nivel de nucleótidos (π: 0,034) como de haplotipo (Hd: 0,863), además de una significativa estructuración de población (fST: 0,761) con un bajo número de migrantes (Nm: 0,157). Las distancias genéticas y las diferencias en los niveles de variabilidad genética entre las tres poblaciones fueron coherentes con una posible subdivisión de población.Conclusión. Este trabajo demostró diferenciación genética entre las poblaciones de T. dimidiata de La Guajira, Cesar y Santander. Se sugiere una posible relación entre tal subdivisión y algunas características eco-epidemiológicas que posee T. dimidiata en el centro-oriente y en el norte de Colombia. Finalmente, este trabajo describe, por primera vez, la utilidad del ND4 como un marcador molecular para el estudio de poblaciones naturales de T. dimidiata.

Introduction. Triatoma dimidiata is the second most important vector of Chagas disease in Colombia after Rhodnius prolixus. Population genetic studies are essential for the adequate design and implementation of vector control and surveillance strategies. Objective. The level of genetic variability and population differentiation was surveyed among three Colombian populations of T. dimidiata from different geographic locations and ecotopes, using ND4 mitochondrial gene. Materials and methods. Genetic comparison was made between two wild populations from La Guajira (n=10) and Santander (n=10) provinces, and one intra (n=15) and one peridomiciliary (n=5) population from the Cesar province. The polymorphism frequencies of the ND4 mitochondrial gene sequence were analyzed to deduce population structure based on the 40 samples. Results. Colombian T. dimidiata showed a high nucleotide (π: 0.034) and haplotype diversity (Hd: 0.863), as well as significant population subdivision (fST: 0.761) and a low migration rate (Nm: 0.157). Genetic distances and variability differences among populations indicate distinct population subdivision amongst the three provinces. Conclusion. ND4 proved useful in elucidating the significant genetic differentiation that has occurred among T. dimidiata populations from La Guajira, Cesar and Santander. The analysis suggested a relationship between population subdivision and some eco-epidemiological attributes of this vector from the central eastern and northwestern regions of Colombia.

The clinical significance of gene polymorphism in children's primary nephrotic syndrome / 国际儿科学杂志

The pathogenesis of children's primary nephrotic syndrome has not been completely clear at present.In the past few years,The polymorphism of these genes,such as angiotensin-converting enzyme gene,apolipoprotein E gene,platelet-activating factor acetylhydrolase gene,human histocompatibility leukocyte antigen gene,glucocorticoid receptor gene and cytokine gene,ect have been discovered that were significantly correlated with susceptibility,pathological progress,steroid response,disease recurrence and prognosis of primary nephrotic syndrome.This article reviewed the research progress of PNS and gene polymorphism.

Association of the monocyte chemoattractant protein-1 -2518A/G gene polymorphism with coronary lesions and in-stent restenosis after percutaneous coronary intervention / 中华老年医学杂志

Objective To investigate the association of monocyte chemoattractant protein-1 (MCP-1) promoter -2518A/G gene polymorphism with coronary lesions and in stent restenosis in Tianjin Chinese population. Methods Two hundred and seventy six patients who underwent percutaneous coronary intervention (PCI) and coronary angiography during follow-up were enrolled in the study. The MCP-1 gene promoter polymorphism at position -2518 was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results The frequencies of three genotypes of MCP-1-2518A/G polymorphism were 21.0% AA, 34. 1% GG,44.9% AG, respectively. There were no statistical differences in the number and the mean degree of stenosis vessels before PCI among 3 genotype groups (all P＞0.05). 113 cases developed in-stent restenosis and 163 cases were free from restenosis. In restenosis group, the AA, AG and GG genotype frequencies were 23.9%, 40.7%, 35.4%, against 19.0%, 47.9% and 33.1% in nonrestenosis group (P = 0. 446) . The frequencies of -2518A and G allele were 44.2%, 55.8% in restenosis group versus 42.9%, 57. 1% in non-restenosis group(P=0. 761). Conclusions The polymorphism of MCP-1-2518 A/G gene may be associated with neither atherosclerosis nor the in-stent restenosis.

Inhibitory effect of triptolide on production of IL -1β from PBMC is associated with IL -1β gene polymorphism / 中国病理生理杂志

AIM: To explore whether the inhibitory effect of triptolide on IL - 1β production by PBMC is asso ciated with IL - 1β gene polymorphisms. METHODS: IL - 1β gene polymorphism was analyzed in 31 healthy volunteers. From genomic DNA, the C - T polymorphism at IL - 1 β - 511 was typed by PCR - RFLP. Meanwhile the IL - 1 β was also measured in the supernatants of the cultured and stimulated peripheral blood mononuclear cells (PBMC) by ELISA. RE SULTS: After LPS stimulation in PBMC cultures of healthy subjects, the secretion levels of IL - 1 β in 9 volunteers who carried IL - 1β -511 T/T genotype were higher than in volunteers who are not T/T genotype (P ＜0.05). Triptolide sup pressed the production of IL - 1β significantly in LPS - treated human PBMC carried C/C and C/T genotype ( P ＜ 0.05 ), but this significant inhibitory effect of triptolide was not seen in T/T genotype ( P ＞ 0.05 ). CONCLUSION: The gene polymorphism at IL - 1β - 511 was related to the production of IL - 1β, and the inhibitory effect of triptolide on the produc tion of IL - 1β was different in C/C, C/T, T/T genotype of IL - 1β -511, which may be one of the reasons for the phe nomenon that people respond differently to triptolide.

Polymorphism analysis of CYP1A1 MspI in ovarian cancer / 吉林大学学报(医学版)

Objective To detect the polymorphism of CYP1A1-MspI gene in patients with ovarian cancer.and discuss the relationship between the polymorphism ofCYP1A1-MspI gene and correspond cases' general materials and clinical materials.Methods The free peripheral blood samples of 81 cases confirmed to be ovarian cancer by postoperative pathology were collected preoperatively and the polymorphism of CYP1A1-MspI gene was detected.The clinical materials of the 81 cases with different genotypes were compared.The relationship between the polymorphism and clinical materials was analyzed.Results Among the 81 cases of ovarian cancer,there were 47 cases of wild type-genotype A(T/T)(58%),25 cases of mutation heterozygosis-genotype B(T/C)(31%),and 9 cases of mutation homozygosis-genotype C(C/C)(11%).The genotypic frequency distribution in patients aged from 12 to 29 was one case of genotype A(2.1%),5 cases of genotype B(20.0%),and no case of genotype C.The genotypic frequency distribution in patients aged from 30 to 49 was 12 case of genotype A(25.5%),8 cases of genotype B(32.0%),and 3 cases of genotype C(33.3%).The genotypic frequency distribution in patients aged from 50 to 69 was 31 case of genotype A(66.0%),8 cases of genotype B(32.0%) and 4 cases of genotype C(44.4%).The genotypic frequency distribution in patients aged more than 70 years was 3 case were of genotype A(6.4%),4 cases of genotype B(16.0%),2 case of genotype C(22.2%).There were significant differences of the ages of onset between patients with different CYP1A1-MspI genotypes (P

Association between MTHFRC677T,CBS844ins68 polymorphism and young ischemic stroke / 吉林大学学报(医学版)

Objective To investigate the genetic association of MTHFRC677T between CBS844ins68 polymorphism and young ischemic stroke.Methods The polymorphism of MTHFRC677T and CBS844ins68 in 98 stroke patients and 116 control subjects were examined and analyzed by using PCR-RFLP.Results The frequencies of two alleles were as follows: T allele 54.09%,C allele 45.91% in patients and T 37.93%,C 62.07% in controls(?2=11.18,P

The Association of Polymorphism of Endothelial Nitric Oxide Synthase Gene in Patients with PAH of Chronic Obstructive Pulmonary Disease / 医学研究杂志

Objective To study the variable number tandem repeats(VNTR)polymorphism in intron 4 of the endothelial nitric oxide synthase(eNos)gene and its relationship with plasma NO in patents with PAH of COPD.Methods The VNTR polymorphism in intron 4of the eNos genes of PAH COPD and healthy control were detected by PCR.The plasma level of NO3-/NO2-was measured by spectrophotometer,which was used as an index of NO synthesis.Data were analyzed according to the different genotype and allelic gene frequency.Results The COPD PAH group significant higher frequency of VNTR 4a allele and 4a/4b allele and 4a/4b+4a/4a genotype than those of the control(P=0.027,P

Genetic polymorphisms of drug-metabolizing enzymes CYP2C19,NAT2, and TPMT in a Han Chinese population from He-nan area / 中国新药与临床杂志

AIM: To determine the distribution and frequency of functionally important allelic variants in the cytochromes P450 (CYP) 2C19, arylamine N-acetyltransferase 2 (NAT2), and thiopurine S-methyltransferase (TPMT) genes in the Han Chinese population and compare them with those of other ethnic populations.METHODS: Genotyping was carried out in a total of 210 unrelated Han Chinese volunteers derived from He-nan area. CYP2C19 variants ( * 2 and * 3), NAT2 variants ( * 6 and * 7), and TPMT variants ( * 3A, * 3B, and * 3C) were detected using polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP)assays. Detection of NA T2 * 5 and TPMT * 2 were performed using allele-specific polymerase chain reaction assays. RESULTS: Allele frequencies of CYP2C19 * 2 and * 3 occurred with 34.76 % and 6.4 %, respectively.Thirty-one persons ( 14.8 % ) carried two of these CYP2C19 alleles responsible for poor metabolizing activity.The frequencies of specif ic NAT2 alleles were 59.1%, 4.1%, 26.4 %, and 9.5 % for * 4 (wild-type), * 5(341C), * 6 (590A), and * 7 (857A), respectively. Genotyping of three different single nucleotide polymorphisms in the NA T2 gene revealed that the frequency of slow acetylators was 19.5 %. TPMT * 3C had an allelic frequency of 1.2 %. TPMT* 2, TPMT * 3A, or TPMT* 3B was not detected in the analysed samples. CONCLUSION: The overview of allele distribution for drug-metabolizing enzymes CYP2C19, NAT2, and TPMT among a Han Chinese population shows obvious difference to Caucasians. The data will be useful for clinical pharmacokinetic investigation and drug dosage administration to Han Chinese population.

Association of the C3435T polymorphism in the multidrug resistance gene 1 and response to antiepileptic drug treatment in epilepsy patients / 中华神经科杂志

Objective To determine the frequency of polymorphism at exon 26 (C3435T) of muhidrug resistance 1 gene (MDR1) in epileptic patients in the southern Chinese and to study the association of this polymorphism with pharmacoresistance.Methods DNA samples were obtained from 134 patients,of whom 72 were resistant to antiepileptic drug treatment and 62 were responsive to the treatment. Genotypes of the C3435T polymorphism were determined by polymerase chain reaction (PCR) followed by restriction digestion and gel electrophoresis.Genotype and allele frequencies in the drug resistant group were compared to those in the response group by Chi-square analysis.Results Of all 134 patients,33 (24.6%) had CC genotype,72 (53.7%) had CT genotype,and 29 (21.6%) had TT genotype.The frequency of CC genotype was significantly higher in the pharmaeoresistance group (33.3%) than that in the responsive group (14.5%,P=0.012).The frequency of the C allele was also significantly higher in the pharmacoresistance group (57.6%) than that in the responsive group (44.4%,P=0.03).When patients were divided by types of seizure into three groups:generalized seizure group,partial seizure group,and undefined seizure group,the CC genotype and C allele were associated with pharmacoresistance in the partial seizure group.Conclusions In the southern Chinese,the CC genotype and C allele are associated with resistance to the antiepileptic treatment.This finding needs to be verified in studies with larger sample size.

Association study between COL3A1 gene polymorphisms and ischemic stroke / 中华神经科杂志

Objective To investigate the characters of the COL3A1 gene polymorphisms in Chinese population of Hunan region and the relationship between the COL3A1 gene polymorphisms and ischemie stroke.Methods Objects examined were composed of 70 healthy controls,110 patients with acute cerebral infarction.The frequencies of the genotypes were detected by using PCR-SSLP techniques and correlated PCR segements were analyzed by directly sequence to detect the COL3A1 gene polymorphisms.Result There were significant differences in the distribution of VNTR with COL3A1 genotype polymorphism between the patients of acute cerebral infarction and healthy controls,the former being 0.93,the latter 0.43,with a significant difference(P

Effect of CYP2A6 genetic polymorphisms on serum concentration of sodium valproate / 中华神经科杂志

Objective To investigate the effect of cytochrome P_ 450 2A6 (CYP2A6) genetic polymorphisms on serum concentration of sodium valproate. Methods A total of 98 epileptic patients receiving sodium valproate after a period of more than 5 half-time were recruited. The genotypes of CYP2A6 of the patients were detected by nested-primer polymerase chain reaction (PCR) to examine the alleles CYP2A6*1 and CYP2A6*4. Fluorescence polarization immunoassay (FPIA) was used to measure the serum concentration of sodium valproate. Results Of the 98 cases, 73 (74.5%) were wild genotypes, 24 (24.5%) were CYP2A6*1/*4 genotypes and 1(1.0%) was CYP2A6*4/*4 genotype. According to the genotypes of CYP2A6 the patients were divided into two groups,one was group A (CYP2A6*1/*1) and the other was group B (CYP2A6*1/*4 or *4/*4). The mean value of the serum concentration of sodium valproate of the patients in group A(4.1393?0.2793) was higher than that in group B(3.3486?0.3919) with a statistical significance (P