Polymorphism of KIR2DL4 gene among northern Chinese Han population / 中国输血杂志

【Objective】 To investigate the polymorphism of KIR2DL4 gene in northern Chinese Han population. 【Methods】 A total of 327 DNA samples were isolated by magnetic beads from unrelated individuals of northern Chinese Han population. The coding sequence (CDS) of KIR2DL4 were amplified using four pairs of KIR2DL4-specific PCR primers developed by our own KIR sequencing-based typing patent, and each exon of KIR2DL4 carried by the four PCR amplicons was then subjected to DNA Sanger sequencing in both directions. The genotype of each sample was assigned using the Assign 4.7 software. 【Results】 Among 327 individuals, 8 different kinds of KIR2DL4 alleles were detected, with observed frequencies ranked as KIR2DL4*00102 [77.1%(252/327)], *00501 [35.8%(117/327)], *011 [20.2%(66/327)], *00602 [12.5%(41/327)], *00801 [8.6%(28/327)], *00103 [4.9%(16/327)], *00503 [1.5%(5/327)] and *00504 [0.9%(3/327)]. In this study, the 10A type alleles which can encode a full membrane-bound receptor include 2DL4*00102, *00103, *00501, *00503, *00504 and *00602, whereas the 9A type alleles which produce truncated forms of receptor include 2DL4*00801 and *011. The observed frequencies for 10A and 9A type KIR2DL4 alleles were 97.6% (319/327) and 27.8% (91/327), respectively. The ratio of 10A to 9A type was 3.5: 1. The observed frequencies of KIR2DL4 alleles in northern Chinese Han population showed no significant difference compared with southern Chinese Han population (P>0.05). 【Conclusion】 The allelic diversity of KIR2DL4 elucidated in the present study can provide valuable data for KIR-associated disease studies and human evolution.

Establishment of a novel Chinese metastatic melanoma cell line and analysis of its biological characteristics / 中华皮肤科杂志

Objective:To establish a melanoma cell line derived from a Chinese female patient of Han nationality with metastatic melanoma, and to study its basic biological characteristics.Methods:Metastatic melanoma cells were isolated from axillary lymph nodes of a 17-year-old female patient with malignant melanoma, and subjected to culture in vitro to establish a cell line. Short tandem repeat (STR) genotyping was performed to compare the information about the cell line and its derived tissue, and to detect gene mutations; cell counting kit-8 (CCK8) assay was conducted to assess the cellular proliferative activity, and soft agar cloning assay to assess the anchorage-independent proliferation; karyotype analysis was performed to determine the number and structure of chromosomes; with the highly aggressive melanoma cell line A2058 and keratinocyte line HaCaT serving as controls, Transwell assay was conducted to detect differences in cell migratory and invasive abilities, cell immunofluorescence assay and Western blot analysis were performed to determine the protein expression of melanoma-specific markers HMB45, S100 and Melan-A; the tumorigenicity was evaluated in vivo in a tumor-bearing mouse model. Results:A melanoma cell line was successfully established and named ZJMM-45, which was cultured for more than 70 passages over a 1-year period, and showed a stable shape and proliferative activity. The cells were spindle-shaped or polygonal, and could produce melanin. STR matching analysis showed that the ZJMM-45 sample was 96% matched with the cryopreserved lymph node tissue of the patient, suggesting that they were from the same source. A tumor-related gene BRAF V600E mutation (c.1799T>A) was identified in the ZJMM-45 cell line; karyotype analysis revealed that ZJMM-45 cells had triploid chromosomes and abnormal structures. ZJMM-45 cells grew exponentially in vitro and reached a plateau-phase in growth on day 5; the cells grew clonally and formed colonies in agar, showing anchorage-independent and malignant proliferative activity. Cell immunofluorescence assay and Western blot analysis showed that both ZJMM-45 and A2058 cells expressed HMB45, S100 and Melan-A; Transwell assay revealed that the numbers of invasive and migratory ZJMM-45 cells (300 ± 14, 260 ± 14, respectively) were significantly higher than those of invasive and migratory A2058 cells (150 ± 6, 160 ± 19, t = 13.25, 11.76, respectively, both P < 0.001) . The tumor-bearing mouse experiment showed that all 5 nude mice developed tumors with an inner diameter of 1.0 cm after 4 weeks, and the tumors were histopathologically characterized by proliferating hyperchromatic melanoma cell nuclei and formation of small nests, which were similar to primary solid tumors. Conclusion:The metastatic melanoma cell line ZJMM-45 derived from a Chinese patient with melanoma was successfully constructed, which carried the BRAF V600E mutation and expressed melanoma-specific markers, and was characterized by rapid proliferation, invasion and metastasis in both in vivo and in vitro culture, as well as obvious tumorigenicity in the in vivo experiment.

Association between self-reported snoring and hypertension among Chinese Han population aged 30-79 in Chongqing, China

BACKGROUND@#We aim to explore the association between self-reported snoring and hypertension among adults aged 30-79 in Chongqing, China.@*METHODS@#A total of 23,342 individuals aged 30-79 were included at baseline from August 2018 to January 2019, and the final sample size for the analysis was 22,423. Face-to-face interviews and physical examinations were conducted by trained investigators. Logistic regression was performed to study age-specific and gender-specific associations between snoring and hypertension.@*RESULTS@#Frequent snoring was associated with the risk of hypertension for each age and gender group, and the frequency of snoring was positively correlated with the risk for hypertension. For the three age groups (< 45, 45-59, ≥ 60), compared with the non-snoring group, those who snore often had a 64.5%, 53.3%, and 24.5% increased risk of hypertension (< 45: OR = 1.65, 95%CI 1.34-2.02; 45-59: OR = 1.53, 95%CI 1.37-1.72; ≥ 60: OR = 1.25, 95%CI 1.09-1.42), respectively. For men and women, those who snore often had a 46.8% and 97.2% increased risk of hypertension, respectively, than the non-snoring group (men: OR = 1.47, 95%CI 1.33-1.63; women: OR = 1.97, 95%CI 1.75-2.23).@*CONCLUSIONS@#People who snore frequently should pay close attention to their blood pressure levels in order to achieve early prevention of hypertension, particularly for snorers who are female and aged under 45; importance should be attached to their blood pressure control.

Association study of zinc finger ZBTB22 single nucleotide polymorphisms and schizophrenia in Han Chinese population / 上海交通大学学报（医学版）

Objective: To explore the association of zinc finger ZBTB22 gene single nucleotide polymorphisms (SNPs) and schizophrenia in Han Chinese population. Methods: A case-control study was designed by genotyping four SNPs (rs3130100, rs1061783, rs1061801 and rs3130099) in 658 schizophrenia patients and 658 healthy controls of Chinese Han origin. SHEsis was used to analyze genotypic and allelic distributions, linkage disequilibrium and haplotype distribution. Results: rs3130100, rs1061783, and rs3130099 showed significant differences between the cases and controls in allele frequencies (P<0. 05 after Bonferroni correction), but no statistically significant differences were found in genotype frequencies after Bonferroni correction. Strong linkage disequilibrium was found among the four SNPs, and the frequency of haplotype TCGA significantly decreased in the schizophrenia patients (P=0.015 after Bonferroni correction). Conclusion: The ZBTB22 SNPs rs3130100, rs1061783 and rs3130099 may be associated with schizophrenia in Han Chinese population.

The correlation of age and the proximal humerus CR image of Chinese Han adults / 中国法医学杂志

Objective To study age-related structural changes of proximal humerusin Chinese Han adults,for the application inage estimation.Methods Shoulder joint computed radiographs(CR) of 210 Chinese Han adults were sampled,with 124 males aging from 18 to 83 years old and 86 females aging 18 to 60 years old.Four observation indexes (the height of humerus bone marrow cavity,the change of trabecular bone in proximal humeral epiphysis,the change of trabecular bone in humeral macronodular and the change of trabecular bone in subacromial-clavicular bone marrow cavity) related with age were observed and scored.The regression equations of age estimation and change scores were established and tested statistically.Results Every index wasclosely correlated with the age changes inadults.The changes of trabecular bone in proximal humeral epiphysis and the changes of trabecular bone in subacromialclavicular bone marrow cavity have much better effects than the height of humerus bone marrow cavity and the changes of trabecular bone in humeral macronodular.The regression equations could predict the age of Chinese Han adults with satisfactory accuracy.Conclusion CR changes of the height of humerus bone marrow cavity,the changes of trabecular bone in proximal humeral epiphysis,the changes of trabecular bone in humeral macronodular and the changes of trabecular bone in subacromial-clavieular bone marrow cavity can bepracticallyusefulin age estimation for Chinese Han adults.

Distribution of Genetic Polymorphisms about CYP2C19 Gene in the Elderly Chinese Han Populations of Guangzhou and the Comparison in Different Populations / 中山大学学报(医学科学版)

[Objective]To investigate the genetic polymorphisms of the CYP2C19 gene in the elderly Chinese Han populations of Guangzhou,and compare the frequencies of CYP2C19 gene polymorphisms in different populations,in order to provide accurate data for the appropriate prescription.[Methods]To detect the genetic polymorphisms of the CYP2C19 gene by the DNA microarray,and compare the frequencies of CYP2C19 gene polymorphisms in Chinese Han populations from different areas and the different races.[Results]There were 2312 case samples in our study. The allele frequencies of CYP2C19*1,CYP2C19*2 and CYP2C19*3 were 64.27%,30.75%,and 4.98%,respectively. As the genotype,EM(*1/*1)was 41.44%(n=958),IM(*1/*2,*1/*3)was 45.67%(n=1056),and PM(*2/*2,*2/*3 and*3/*3)was 12.89%(n=298). The ratios of EM and IM in Chinese Han populations from different areas and all the subtypes of the CYP2C19 genotype in different minority were statistically significant. As the races,there were difference in all the subtypes of the CYP2C19 genotype when Asian populations were compared with white races(P<1304.64)and black races(P<0.01),which was also statistically significant.[Conclusions]The distributions of the CYP2C19 gene polymorphisms were significantly different in Chinese han populations and in different races,and the main subtypes of the CYP2C19 genotype in the elderly of Chinese han populations were IM and EM,which is beneficial for prescribing appropriate in the elderly populations.

Cable Pin System versus K-wire Tension Band Fixation for Patella Fractures in Chinese Han Population: A Meta-analysis / 华中科技大学学报（医学）（英德文版）

This meta-analysis compared the therapeutic effect of cable pin system (CPS) with K-wire tension band (KTB) in the treatment of patella fractures among Chinese Han population.The databases of PubMed,Cochrane library,China National Knowledge Infrastructure (CNKI),Chinese WanFang and Chinese VIP were searched for studies on CPS versus KTB in the treatment of patella fractures among Chinese Han population.Literatures were screened according to the inclusion and exclusion criteria.The quality of the studies was assessed,and meta-analysis was performed using the Cochrane Collaboration's REVMAN 5.3 software.A total of 932 patients from 15 studies were included in this meta-analysis (426 fractures treated with CPS and 506 fractures treated with KTB).There were significant differences in duration of hospital stay [mean difference (MD)=-1.07;95％ confidence interval (CI):-1.71 to-0.43],fracture healing time (MD=-l.23;95％ CI:-1.68 to-0.77),flexion degree of knee joint at 6th month after operation (MD=14.82;95％ CI:10.93 to 18.71),incidence of postoperative complication [risk ratio (RR)=0.16;95％ CI:0.09 to 0.27] and excellent-good rate of B(o)stman score (RR=1.09;95％ CI:1.03 to 1.16) between the CPS group and KTB group,while no significant difference was found in operative time between the two groups (MD=-4.52;95％ CI:-11.70 to 2.67).For the treatment of patella tractures among Chinese Han population,limited evidence suggests that the CPS is more suitable than the KTB when considering the hospital stay,fracture healing time,flexion degree of knee at 6th month after operation,incidence of postoperative complication and excellent-good rate of B(o)stman joint score.Due to the limitation of high quality evidence and sample size,more large-scale randomized controlled trials are needed to validate the findings in the future.

Genetic polymorphism for 124 Individual Identiifcation SNPs from Chinese Han using Ion PGM? platform / 中国法医学杂志

ObjectiveTo investigate the polymorphisms of 124 individual identiifcation SNPs in Chinese Han using the Ion Personal Genome Machine?(PGMTM).Method Samples from 130 unrelated Chinese Han individuals and two families (8 genealogical individuals) were ampliifed using Ion AmpliseqTM Library kit and sequenced on Ion Torrent PGM? platform.Results 14 148 SNPs were detected.A total of 99.992 9% SNPs were correctly called by the HID SNP Genotyper v4.3 plugin, while 0.007 1% wrongly reported and 62 NN calls needed manual correction. The MP ranged from 0.348 0 (rs2831700) to 0.817 3 (rs740910) with the value of 6.898 4 × 10-34 for CMP. The DP ranged from 0.182 7 (rs740910) to 0.652 0 (rs1355366) with the value of 0.999 999 999 999 999 999 999 999 999 999 999 310 2 for CDP, which was larger than that of 22 STR loci. The PE ranged from 0.007 3 (rs1024116) to 0.278 1 (rs1058083) with the value of 0.999 999 616 7 for CPE, which was smaller than that of 22 STR loci. A total of 8 Y-SNP haplo-types were observed from 72 unrelated male samples. No mutation was observed from pedigrees.Conclusion The 124 IISNPs were high polymorphic in Chinese Han and they were ideal markers for human identiifcation. The PGMTM platform has a potential role in forensic science.

Single nucleotide polymorphisms predisposing to asthma in children of Mauritian Indian and Chinese Han ethnicity

Our objective was to investigate the distributions of six single nucleotide polymorphisms (SNPs) MS4A2 E237G, MS4A2 C-109T, ADRB2 R16G, IL4RA I75V, IL4 C-590T, and IL13 C1923T in Mauritian Indian and Chinese Han children with asthma. This case-control association study enrolled 382 unrelated Mauritian Indian children, 193 with asthma and 189 healthy controls, and 384 unrelated Chinese Han children, 192 with asthma and 192 healthy controls. The SNP loci were genotyped using polymerase chain reaction (PCR)-restriction fragment length polymorphism for the Chinese Han samples and TaqMan real-time quantitative PCR for the Mauritian Indian samples. In the Mauritian Indian children, there was a significant difference in the distribution of IL13 C1923T between the asthma and control groups (P=0.033). The frequency of IL13 C1923T T/T in the Mauritian Indian asthma group was significantly higher than in the control group [odds ratio (OR)=2.119, 95% confidence interval=1.048-4.285]. The Chinese Han children with asthma had significantly higher frequencies of MS4A2 C-109T T/T (OR=1.961, P=0.001) and ADRB2 R16G A/A (OR=2.575, P=0.000) than the control group. The IL13 C1923T locus predisposed to asthma in Mauritian Indian children, which represents an ethnic difference from the Chinese Han population. The MS4A2 C-109T T/T and ADRB2 R16G A/A genotypes were associated with asthma in the Chinese Han children.

Pharmacokinetics of doxapram injection in Chinese Han, Mongolian, Korean, Uigur and Hui healthy subjects / 中国药理学通报

Aim To investigate and compare the phar-macokinetics of doxapram injection in healthy subjects of different Chinese nationalities including Han, Mon-golian, Korean, Hui and Uigur, and the influence of gender,in order to provide instruction and help for the usage of doxapram for both clinic and remedy of battle wound. Methods An HPLC-UV method was used to determine the plasma concentration of doxapram. Fifty healthy subjects ( five males and five females of each nationality) were recruited for the study. A single dose of 50 mg doxapram was administered intravenously to the healthy subjects, and blood samples were collected at various predetermined time points. The pharmacoki-netic parameters were calculated by DAS software and were compared by SPSS 13. 0 software, in order to as-sess the influence of nationality or gender on pharmaco-kinetics of doxapram. Results The results indicated that the pharmacokinetic profile of doxapram in vivo could be described as two-compartment model. The main pharmacokinetic parameters for Han, Mongolian, Korean, Hui and Uygur were as follows: Cl ( 0. 25 ± 0. 11 ) , ( 0. 33 ± 0. 11 ) , ( 0. 27 ± 0. 07 ) , ( 0. 26 ± 0. 06) and (0. 39 ± 0. 25) L·h-1 ·kg-1 , while Cmax (1. 55 ± 0. 52 ) , ( 1. 02 ± 0. 30 ) , ( 1. 31 ± 0. 47 ) , (1. 48 ± 0. 46 ) and ( 0. 99 ± 0. 35 ) mg · L-1 . The AUC0-12. 5 , AUC0-∞ and Cmax of Chinese Han were sig-nificantly higher than those of Uigur and Mongolian ( P0. 05 ) . There were statistically significant differences in Vc , Vd and CL between young males and females ( P < 0. 05 ) . Conclusion The large inter-individual variation in the main pharmacoki-netics suggests the dosage of doxapram should be ad-justed for different nationalities for both clinic and rem-edy of battle wound.

Population pharmacokinetics of doxapram in five different Chinese ethnic groups / 中国药学杂志

OBJECTIVE: To construct a population pharmacokinetic (PPK) model of doxapram in five different ethnic groups including Han, Mongolian, Korean, Hui and Uigur by NONMEM. METHODS: Fifty healthy volunteers were given a single dose of 50 mg doxapram intravenously. Blood samples were collected and determined by HPLC with a UV detector. Population pharmacokinetic model was constructed by NONMEM software. The influences of fixed-effect factors on the PK parameters were investigated. RESULTS: The following population parameters were estimated with a three-compartment model: CL1 of 17.8 L · h-1, CL2 of 10.5 L · h-1, CL3 of 85.2 L · h-1, V1 of 17.4 L, V2 of 62.6 L, and V3 of 16.8 L. Ethnic group has a significant effect on V2, CL3 and CL1, while gender has a significant effect on CL2. CONCLUSION: The final PPK model of doxapram established by NONMEM is robust and reliable. It may be beneficial for the clinical use of doxapram. Copyright 2013 by the Chinese Pharmaceutical Association.

SNPs discovery and linkage disequilibrium analysis of BSG in Chinese Han population / 中南大学学报(医学版)

Objective:To identify BSG single nucleotide polymorphisms (SNPs) in Chinese Han population. Methods:Peripheral blood samples were collected from 48 unrelated healthy Chinese Han subjects. Sequences at the BSG locus, including the promoter region, all exons and exon-intron boundaries were ampliifed, sequenced and followed by Hardy-Weinberg equilibrium test and linkage disequilibrium (LD) analysis. Results:A total of 19 SNPs were identiifed, 2 of which two were novel. Genotype distributions of all SNPs were consistent with Hardy-Weinberg equilibrium. Four haplotype blocks were constructed throughout the gene locus, and 9 haplotype tag SNPs (htSNPs) were inferred. Distribution of SNPs was in accordance with the neutrality theory in Chinese Han population. Conclusion:For the ifrst time, systematic identiifcation of BSG SNPs in the Chinese Han population has been done, and 9 htSNPs are identified. Our study has provided basis for further genetic association studies for related diseases as wel as pharmacogenetics study for drug response in Chinese Han population.

Pharmacokinetcs of single dose cefepime injection in Chinese Han, Mongolia, Korean, Uigur, and Hui healthy volunteers / 中国药学杂志

OBJECTIVE: To investigate and compare the pharmacokinetics of cefepime in healthy volunteers of different Chinese nationalities (Han, Mongolia, Uigur, Korea, and Hui) and different genders, thus to provide instruction and help for using cefepime safely, rationaly and effectively in both ordinary clinic and remedy of battle wound. METHODS: A single dose of 1.0 g cefepime was given by intravenous infusion under fasting condition to ten healthy volunteers (five males and five females) of each Chinese nationality. Plasma samples were obtained before dosing and at various predetermined time points after the dosing, and the plasma concentrations were determined by a validated HPLC-UV method. The pharmacokinetic parameters were calculated by DAS2.0 software and were compared by SPSS11.5 software. RESULTS: The PK parameters of cefepime in Han, Mongolia, Uigur, Korea and Hui nationalities after a single intravenous administration of 1.0 g were as follows: t1/2β (1.97 ± 0.20), (2.10 ± 0.33), (2.06 ± 0.33), (2.40 ± 0.65), and (1.94 ± 0.24) h; AUC0-β (139.69 ± 23.78), (153.92 ± 22.79), (165.58 ± 24.49), (142.11 ± 29.77), and (132.78 ± 23.79) mg · h · L-1;ρmax(68.75 ± 10.41), (78.22 ± 13.87), (83.19 ± 10.31), (73.82 ± 9.59), and (62.91 ± 10.09) mg · L-1 , respectively. The PK parameters of cefepime in 25 male volunteers and 25 female volunteers after a single intravenous administration of 1.0 g were as follows: t1/2β (2.06 ± 0.54) and (2.13 ± 0.44)h; AUC0-β (134.06 ± 22.33) and (158.68 ± 24.85)mg · h · L-1;ρmax (66.94 ± 9.14) and (78.95 ± 12.71)mg · L-1, respectively. Results of ANOVA and Kruskal-Wallis rank test showed that there were no significant differences in the PK parameters Vd, CL, InAUC, and t1/2β of different nationalities and in Vd and t1/2β of different genders, but there were significant differences in lnρmax of different nationalities and CL, InAUC, and lnρmax of different genders. Then, it was found there was high linear correlation( P < 0.01) between body weight and CL, InAUC and lnρmax. The differences of the above PK parameters became insignificant after normalization by body weight. CONCLUSION: When cefepime is given in doses based on body weight, its pharmacokinetics has no significant differences among five nationalities and between genders. Copyright 2012 by the Chinese Pharmaceutical Association.

Study on the references regarding height and prevalence of stunting among children and adolescents aged 7 to 18 years of Chinese Han ethnicity / 中华流行病学杂志

Objective To develop the reference on height among children and adolescents aged 7 to 18 years of Chinese Han ethnicity in different administrative districts of China and to use this height reference for screening stunting.Results from the national screening program were compared with the WHO references.Methods Data from the Chinese National Survey on Students Constitution and Health in 2005 was used to develop the height references through LMS method.Results Differences among the references on height for children and adolescents in different districts ( Ⅰ - Ⅳ ) were remarkable.The highest was seen in the Second Districts while the lowest was seen in the First Districts among those at the age of 18,with differences as 3.18 cm for boys and 2.92 cm for girls.The heights from the inland were shorter than that of the WHO references,with the differences ranging from 0.31 cm to 5.07 cm for boys,and from 0.98 cm to 4.22 cm for girls.The prevalence rates of stunting were 2.22％,2.29％,5.25％,respectively according to local references,national references and the WHO references.Conclusion Universal height references from the whole nation could not discriminate the variations caused by geographic conditions and hereditory factors related to socio-economie situations.Height references should be developed locally,to evaluate height levels of the areas.

Polymorphisms in the interleukin-1 receptor-associated kinase 4 gene are associated withsusceptibility to severe sepsis / 中华急诊医学杂志

Objective To investigate the possible association of IRAK4 polymorphisms with susceptibility to and prognosis of severe sepsis.Methods A total of 192 patients hospitalized in emergency department of Zhongshan Hospital from February 2006 to December 2009,and another 192 healthy volunteers were enrolled in this case-control study.Patients were excluded if they had metastatic tumors,autoimmune diseases,AIDS or received immunosuppressive drugs.This study was approved by the ethical committee of Zhongshan Hospital,Fudan University.Sepsis patients were divided into survival group(n =124)and non-survival group(n =68)according to the 30-day mortality.Primer 3 software was used to design the PCR and sequencing primers.Genomic DNA was extracted from peripheral blood mononuclear cells.Seven tagSNPs were selected based on the data of Chinese Han in Beijing from the Hapmap projectand genotyped by direct sequencing.We used x2 analysis to evaluate the significance of differences in genotype and allele frequencies between different groups.Results The distributions of all tagSNPs were consistent with Hardy-Weinberg equilibrium.The allele and genotype frequencies of rs4251545(G/A)were significantly different between severe sepsis and healthy control groups(P =0.015,P =0.035,respectively).Carriers of the rs4251545A had a higher risk for severe sepsis compared with carriers of the rs4251545G(OR =1.69,95％ CI:1.10-2.58).The allele and genotype frequencies of all SNPs were not significantly different between survivor group and non-survivor group.Conclusions These findings indicated that the variants in IRAK4 are significantly associated with severe sepsis susceptibility in the Chinese Han population.

The genetic association study of dendritic cell immunoreceptor polymorphisms in anti-CCP antibodynegative rheumatoid arthritis in Chinese Han population / 中华风湿病学杂志

ObjectiveThis work is aimed to investigate the possible association of dendritic cell immunoreceptor (DCIR) with rheumatoid arthritis (RA) susceptibility in Chinese Han population.Methods A total of 523 patients with RA and 510 healthy controls were genotyped for single-nucleotide polymorphism (SNP) rs2377422 and rs10840759.Association analyses were performed on the whole data set and on RA subsets based on the status of anti-cyclic citrullinated peptide antibody (CCP) in RA patients.Finally,we carried out the association analysis of rs2377422 with DCIR mRNA expression in RA patients.Statistical analysis used in this study included X2 test,Logistic regression,and Mann-Whitney U test.ResultsDCIR rs2377422 was found significantly associated with RA(allele analysis: OR 1.26; 95％CI 1.06～1.51,P=0.005; genotype analysis CC vs TT+TC: OR 1.34; 95％CI 1.18～2.06,P=0.004).Following stratification for anti-CCP antibody status,association of ra2377422 with anti-CCP-positive RA was observed(allele analysis: OR 1.22,95％CI 0.99～1.48,P=0.055).In contrast,the SNP rs2377422 was found specifically susceptible to anti-CCP-negative RA(allele analysis: OR 1.46; 95％CI 1.10～1.93,P=0.0091; genotype analysis CC vs TT+TC: OR 1.58;95％CI 1.01～2.47,P=0.043),despite loss of power in the analysis.DCIR gene transcription quantification analysis further proved the dominant effect of rs2480256 CC genotype on DCIR mRNA expression levels in RA patients (CC vs TT+TC: 0.429±0.069 vs 0.238±-0.023,U=1861,P=0.0015).ConclusionThe study provides evidence for the association between DCIR rs2377422 and RA,particularly with anti-CCP-negative RA in Chinese Han populations.

Association of genetic variants in the IRAK-4 gene with susceptibility to severe sepsis / 世界急诊医学杂志（英文）

BACKGROUND: The association of genetic variation in the IRAK-1 gene with sepsis outcome has been proved. However, few studies have addressed the impact of the IRAK-4 gene variants on sepsis risk. This study aimed to determine whether the polymorphisms in the IRAK-4 gene are associated with susceptibility to and prognosis of severe sepsis in the Chinese Han ethnic population.METHODS: In this case-control study, 192 patients with severe sepsis hospitalized in the emergency department of Zhongshan Hospital from February 2006 to December 2009 and 192 healthy volunteers were enrolled. Exclusion criteria included metastatic tumors, autoimmune diseases, AIDS or treatment with immunosuppressive drugs. This study was approved by the ethical committee of Zhongshan Hospital, Fudan University. Sepsis patients were divided into a survival group (n=124) and a non-survival group (n=68) according to the 30-day mortality. Primer 3 software was used to design PCR and sequencing primers. Genomic DNA was extracted from peripheral blood mononuclear cells. Seven tagSNPs in IRAK-4 were selected according to the data of the Chinese Han population in Beijing from the Hapmap project and genotyped by direct sequencing. The chi-square test was used to evaluate the differences in genotype and allele frequencies between the two groups.RESULTS: The distributions of all tagSNPs were consistent with Hardy-Weinberg equilibrium. The allele and genotype frequencies of rs4251545 (G/A) were significantly different between the severe sepsis and healthy control groups (P=0.015, P=0.035, respectively). Carriers of the rs4251545A had a higher risk for severe sepsis compared with carriers of the rs4251545G (OR=1.69, 95％ CI: 1.10-2.58). The allele and genotype frequencies of all SNPs were not significantly different between the survival group and non-survival group.CONCLUSION: These findings indicate that the variants in IRAK-4 are significantly associated with susceptibility to severe sepsis in the Chinese Han ethnic population.

Effects of SNPs at Newly Identified Lipids Loci on Blood Lipid Levels and Risk of Coronary Heart Disease in Chinese Han Population: A Case Control Study / 华中科技大学学报（医学）（英德文版）

Associations between “lipid-related” candidate genes,blood lipid concentrations and coronary artery disease (CHD) risk are not clear.We aimed to investigate the effect of three newly identified lipids loci from genome-wide association studies on CHD and blood lipid levels in Chinese Han population.The genotypes of SNPs at three newly identified lipid loci and blood lipids concentrations were examined in 1360 CHD patients and 1360 age- and sex-frequency matched controls from an unrelated Chinese Han population.Allele T of rs16996148 occurred less frequently in CHD patients with the odds ratio (OR) being 0.64 (95％ CI 0.50 to 0.81),after adjusting for conventional risk factors and was associated with a 33％ decreased CHD risk (P＜0.01) comparing with the major allele G.Individuals with GT genotype had the lowest CHD risk.No associations were found between the polymorphisms of other two loci with CHD risk and all three SNPs had no effect on lipid profile in this population.SNP rs16996148 on chromosome 19p13 is significantly associated with lower risk for CHD in Chinese Han population.However,it remains unresolved why these lipid-related loci had significantly less effects than the correspondingly expected effects on blood lipids levels in this population.

Identification of Common Variants within KCNK17 in Chinese Han Population / 华中科技大学学报（医学）（英德文版）

KCNK17 is a member of the acid-sensitive subfamily of tandem pore K+channels,which are open at all membrane potentials and contribute to cellular resting membrane potential.Recent genome-wide study(GWA)has shown that variants within KCNK17 confer genetic susceptibility for increasing ischemic stroke.In an effort to discover additional polymorphism(s),we scrutinized the genetic polymorphisms in the KCNK17.By direct DNA sequencing in 32 individuals,we identified nine sequence variants within the 16 kb of whole KCNK17 gene: one in exonl,one in intron and seven in the promoter region.Haplotypes,their frequencies and linkage disequilibrium coefficients(D'),among polymorphisms were estimated.All the polymorphisms in the 5'-flanking region(SNP2-SNP7)being in complete(or nearly complete)association with each other in the promoter region maybe produce synergistic effect to regulate the expression of KCNK17 gene and then have an influence on the pathogenesis of cerebrovascular diseases.The common haplotypes were observed comprising 88.9% of the total haplotypes in the same block.Bioinformatic analysis predicted several potential transcriptional factors binding sites by SNP-95,-134,-596 and-846.However,these binding sites need to be experimentally verified.The information concerning genetic polymorphisms of KCNK17 gene might provide valuable information for future genetic studies of diseases.

Identification of 5 Novel Y Chromosome STR Loci and Haplotype Distribution in Chinese Han Population (Guangzhou) / 中山大学学报(医学科学版)

[Objective] To screen and identify the new Y-STR loci from the Y chromosome and examine the polymorphism of these Y-STR loci. [Method] To seek and locate the position of 5 Y-STR loci, including DYS709, DYS720, DYS721, DYS722, and DYS723, and perform sequencing of these 5 Y-STR loci. Then to investigate the polymorphism in unrelated Chinese Han males. [Results] Five Y-STR loci were identified from Y chromosome sequence. By scrutinizing the physical position on Y chromosome of previously reported Y-STRs, we found that three loci were novel and two loci overlapped with two loci published only online. All loci could be male-specifically amplified with a product size ranging from 185 bp to 278 bp. After 108 males of the Chinese Han Population (Guangzhou) were examined, we found 5 DYS709, 11 DYS720 alleles, 4 DYS721 alleles, 6 DYS722 alleles, and 6 DYS723 alleles. A total of 95 haplotypes were identified, 84 of which were unique, and with a haplotype diversity of 0.997 2±0.001 2(HD±SE). [Conclusion] This set of Y-STRs can be used as Y chromosome genetic makers in related fields.