Interleukin-17A gene variants and risk of coronary artery disease:a large angiography-based study

Background Recent studies have also revealed that interleukin(IL)-17A plays a key role in atherosclerosis and its complication,but the relationship of its common variants with coronary artery disease(CAD) has not been extensively studied.Methods We systematically screened sequence variations in the IL17A gene and designed an angiog-raphy -based case-controlled study consisting of 1031 CAD patients and 935 control subjects to investigate the association between the selected polymorphisms of IL-17A gene and CAD risk in Chinese Han population.Results Frequencies of IL17A rs8193037 GG homozygote and G allele were significantly higher in the patient group than those in the control group(P<0.001;OR=0.68;95%CI=0.54-0.85).Stratification analysis showed that the IL17A rs8193037 G allele significantly increased the risk of CAD only among male subjects (P=0.001;OR=0.63;95%CI=0.47-0.83).After adjustment for conventional risk factors,binary logistic regression analysis showed that the G allele carriers(GG +AG) had significantly increased CAD risk compared with the AA homozygotes (adjusted P<0.001;OR 0.43;95%CI,0.33- 0.58).ELISA showed augmented IL17A production in plasma of the AMI patients.Conclusions Based on our data,we speculated that the SNP rs8193037 of IL17A gene is significantly associated with CAD risk in Chinese Han population and the rs8193037 G allele which is associated with increased expression of IL17A in AMI patients may be an independent predictive factor for CAD.     

程序性细胞凋亡基因单核苷酸多态性与慢性乙型肝炎患者干扰素早期病毒学应答的相关性

Objective To investigate the relationship between the single nucleotide polymorphisms (SNP) of programmed cell death-1 (PD-1) gene and early virologic response of interferon-α (IFN-α) in patients with chronic hepatitis B (CHB). Methods A total of 135 CHB patients were prospectively enrolled in this study. SNP of PD-1.1 and PD-1.2 genes were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in these patients.Then its relationship with early virologic response to IFN-α treatment was analyzed. The data were analyzed by x2 test. Results Among the 135 patients, 33 (24.4%) achieved early virologic response to IFN-α. There were 35, 77, and 23 patients with AA, AG, GG genotgpe of PD-1.1. The early virologic response was achived in 5(14.3%), 25(32.5%) and 3(13.0%) among patients with AA,AG, GG genotypes of PD-1.1, respectively. There were statistically different (x2 = 6. 258, P =0. 044). The subjects with AG genotype showed higher response rate than those with AA or GG genotypes (x2 = 6. 246, P= 0. 012). However, the early virologic response rates were not significant different among subjects with AA, AG or GG genotype of PD-1. 2 ( x2= 3.957, P= 0. 138).Conclusion SNP of PD-1.1 gene may be used as a marker to predict the early virologic response to IFN-α treatment in Chinese CHB patients.     

程序性细胞凋亡基因单核苷酸多态性与慢性乙型肝炎患者干扰素早期病毒学应答的相关性

Objective To investigate the relationship between the single nucleotide polymorphisms (SNP) of programmed cell death-1 (PD-1) gene and early virologic response of interferon-α (IFN-α) in patients with chronic hepatitis B (CHB). Methods A total of 135 CHB patients were prospectively enrolled in this study. SNP of PD-1.1 and PD-1.2 genes were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in these patients.Then its relationship with early virologic response to IFN-α treatment was analyzed. The data were analyzed by x2 test. Results Among the 135 patients, 33 (24.4%) achieved early virologic response to IFN-α. There were 35, 77, and 23 patients with AA, AG, GG genotgpe of PD-1.1. The early virologic response was achived in 5(14.3%), 25(32.5%) and 3(13.0%) among patients with AA,AG, GG genotypes of PD-1.1, respectively. There were statistically different (x2 = 6. 258, P =0. 044). The subjects with AG genotype showed higher response rate than those with AA or GG genotypes (x2 = 6. 246, P= 0. 012). However, the early virologic response rates were not significant different among subjects with AA, AG or GG genotype of PD-1. 2 ( x2= 3.957, P= 0. 138).Conclusion SNP of PD-1.1 gene may be used as a marker to predict the early virologic response to IFN-α treatment in Chinese CHB patients.     

Association of Fas-670 gene polymorphism with inflammatory bowel disease in Chinese patients

AIM: Recent studies suggest that Fas-mediated apoptosis is involved in the pathogenesis of inflammatory bowel disease (IBD). It has been hypothesized that either increased apoptosis of intestinal epithelium or decreased apoptosis of lamina propria lymphocytes may induce inflammation of' gut. The aim of this study was to determine whether the Fas gene promoter polymorphism at position-670 was associated with IBD in Chinese patients. METHODS: Fifty unrelated Chinese patients with IBD (38 patients with ulcerative colitis and 12 with Crohn's disease) and 124 healthy controls were genotyped for the Fas-670 polymorphism by PCR-restriction fragment length polymorphism method. The PCR product was digested by Mva I restriction enzyme. RESULTS: Distribution of the Fas-670 gene polymorphism was 33% for the AA genotype, 52% for the AG genotype and 15% for the GG genotype in 124 healthy subjects. In patients with IBD, 30% was for the AA genotype, 42% for the AG genotype and 28% for the GG genotype respectively. However, there was no significant difference in the genotype (P= 0.1498), allele frequencies (P= 0.3198) and carriage frequencies (P = 0.4133) between healthy controls and IBD patients. Furthermore, we did not find any difference between the left-sided colitis and total colitis (P = 0.8242). CONCLUSION: Fas-670 polymorphism is not associated with IBD in Chinese patients.     

鸟氨酸脱羧酶抗酶抑制因子1多态性与乙型肝炎肝硬化的关系

目的 研究一种高加索人群丙型肝炎肝硬化风险评分模型(cirrhosis risk score,CRS)相关基因的多态性与中国人群乙型肝炎肝硬化的关系,评估该模型在乙型肝炎肝硬化中的应用价值.方法 用基质辅助激光解析电离飞行时间质谱法检测相关的11个单核苷酸多态性位点,研究人群包括肝硬化组患者和对照组无肝硬化表现者,分析各位点与肝硬化的关系,比较肝硬化组和对照组CRS值的差异.用x2检验检测哈维平衡验证样本的群体代表性.两组计量资料的比较用t检验或Wilcoxon秩和检验.单个单核昔酸多态性基因型等分类数据与肝硬化发生的关系用Pearson x2检验,差异有统计学意义的单核苷酸多态性位点进一步用Logistic回归分析判断在显性模型、隐性模型和加性模型下基因型与肝硬化发生的关系,计算比值比及95%可信区间,比值比经性别和年龄校正.结果 鸟氨酸脱羧酶抗酶抑制因子1基因的rs2679757位点与肝硬化的发生相关(x2=6.79,P＜0.05),与AA纯合子相比,携带危险等位基因G的GG+AG基因型显著增加肝硬化的发生风险,比值比为1.63,95%可信区间为1.13～2.35.位于Toll样受体4基因的rs4986791位点和鸟氨酸脱羧酶抗酶抑制因子1基因的rs62522600位点在中国人群中无多态性基因型.其他研究位点与肝硬化的发生无相关性(P＞0.05).肝硬化组和对照组的CRS中位数分别为0.57和0.62,两组比较,差异无统计学意义(P＞0.05).结论 鸟氨酸脱羧酶抗酶抑制因子1多态性rs2679757与乙型肝炎肝硬化的发生相关.高加索人群CRS模型相关的两个多态性位点在中国人群中缺乏多态性,该CRS对评估有无乙型肝炎肝硬化的发生无明显价值,其他多态性位点仍需进一步临床验证.

Abstract：

Objective A cirrhosis risk score (CRS) comprised of single nucleotide polymorphisms (SNPs) in seven genes that predicts the risk of cirrhosis in Caucasian hepatitis C has been reported. The present study was to evaluate the association of 11 separate but related SNPs and the CRS with cirrhosis risk in Chinese hepatitis B patients. Methods A total of 563 Chinese subjects with persistent HBV infection (349 with evident liver cirrhosis and 214 without cirrhosis clinically or pathologically) were studied. The candidate SNPs were detected with a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) method. The allele frequency and genotype distribution of each polymorphism as well as the CRS value within the cirrhosis and non-cirrhosis subjects were compared. Results The rs2679757 polymorphism of the antizyme inhibitor 1 (AZIN 1) gene was associated with the risk of cirrhosis ( x 2 = 6.79,P = 0.03, odds ratio for GG+AG versus AA = 1.63, 95% confidence interval = 1.13-2.35). A gene variant (rs886277) in the transient receptor potential cation channel subfamily M, member 5 gene (TRPM5) was associated with liver cirrhosis, but did not reach statistical significance ( x 2 = 5.77, P = 0.06). Two SNPs (rs4986791, rs62522600) are not polymorphic in Chinese. Genotype frequencies of other SNPs were not different between the cirrhosis and non-cirrhosis groups. The overall CRS values were not different between the cirrhotic and non-cirrhotic groups (median value 0.57 versus 0.62, Z = -1.05, P = 0.29). Conclusions SNP rs2679757 in the AZIN1 gene is associated with the risk of HBV-related liver cirrhosis in Chinese. The CRS for Caucasian population has limited applicability for predicting liver cirrhosis in Chinese hepatitis B patients. SNPs associated with cirrhosis prognosis in hepattis B patients and liver diseases with other etiologies warrant further clinical validation.     

Interleukin-21 gene polymorphisms and chronic hepatitis B infection in a Chinese population

AIM: To investigate the relationship between inter-leukin-21(IL21) gene polymorphisms and chronic hepatitis B virus(HBV) infection in a Chinese population. METHODS: In this case-control study, 366 Chinese HBV-infected patients were recruited and divided into hepatocellular carcinoma(HCC; n = 94) and non-HCC(n = 272) groups at The First Affiliated Hospital of Sun Yat-Sen University, from April 2009 to December 2012. In the non-HCC group, the patients were classified into three clinical subsets, 76 patients had chronic hepatitis B, 101 were HBV carriers and 95 patients had HBV-related cirrhosis. Two hundred eight unrelated healthy controls were also included. Genomic DNA was extracted from peripheral blood. Single nucleotide polymorphisms(SNPs) rs13143866, rs2221903, and rs907715 were subsequently genotyped using the SNaP shot SNP technique.RESULTS: There were no significant differences in allele and genotype frequencies of SNPs rs13143866, rs2221903, and rs907715 between chronic HBVinfected patients and control subjects. Furthermore, no significant differences were found in the frequencies of all alleles and genotypes between the HCC group and the non-HCC group. However, in the subgroup analysis, IL21 rs13143866 genotype AA frequency in the HBV carrier group was higher than in controls(OR = 6.280, 95%CI: 1.238-31.854; P = 0.019), and the effect of the recessive model(AA vs GG + GA, OR = 6.505, 95%CI: 1.289-32.828) was observed in the HBV carrier group. IL21 rs2221903 genotype TC frequency in the HBV carrier group was higher than in controls(OR = 1.809, 95%CI: 1.043-3.139; P = 0.035). In the haplotype analysis, the ATA haplotype(rs13143866, rs2221903, and rs907715) of IL21 was more frequent in the HCC group than in the non-HCC group(0.165 vs 0.104, P = 0.044; OR = 1.700, 95%CI: 1.010-2.863).CONCLUSION: Genotypes rs13143866 AA and rs2221903 TC are risk factors for carrying HBV; ATA haplotype increases the risk of HBV-related HCC onsetin a Chinese population.     

Association of interleukin-10 polymorphisms with risk of irritable bowel syndrome:A meta-analysis

AIM:To clarify the current understanding of the association between interleukin-10(IL-10)polymorphisms and the risk of irritable bowel syndrome(IBS).METHODS:We searched for studies in any language recorded in PubMed,Embase and Cochrane library before August 2013.The associations under allele contrast model,codominant model,dominant model,and recessive model were analyzed.The strengths of the association between IL-10 polymorphisms and IBS risk were estimated using odds ratios(OR)with 95%confidence interval(CI).Fixed effects model was used to pool the result if the test of heterogeneity was not significant,otherwise the random-effect model was selected.RESULTS:Eight case-control studies analyzing three single-nucleotide polymorphisms rs1800870(-1082 A/G),rs1800871(-819C/T),and rs1800872(-592A/C)of the IL-10 gene,which involved 928 cases and 1363 controls,were eligible for our analysis.The results showed that rs1800870 polymorphisms were associated with a decreased risk of IBS(GG+GA vs AA:OR=0.80,95%CI:0.66-0.96),(AA+GA vs GG:OR=0.68,95%CI:0.52-0.90).Subgroup analysis revealed such association only existed in Caucasian ethnicity(AA+GA vs GG,OR=0.70,95%CI:0.55-0.89).The rs1800872 polymorphisms were associated with an increased risk of IBS in Asian ethnicity(CC vs GG:OR=1.29,95%CI:1.01-1.16).There were no associations between rs1800871 polymorphisms and the IBS risk.CONCLUSION:The results suggest that IL-10 rs1800870confers susceptibility to the risk of IBS in Caucasian ethnicity,and the rs1800872 may associate with IBS risk in Asians.However,no significant associations are found between rs1800871 and IBS risk.     

Interferon-λ-related genes and therapeutic response in Chinese hepatitis C patients

AIM: To determine the association between rapid viral response and IL28 B, IL28 RA, IL10 RB and Mx A polymorphisms in the Chinese Han population.METHODS: The study cohort consisted of 238 chronic hepatitis C patients treated with interferon(IFN)-α-2b and ribavirin. Six single nucleotide polymorphisms were genotyped using the ABI Taq Man allelic discrimination assay. Biochemical indices were measured at baseline. Serum hepatitis C virus(HCV) RNA was detected at weeks 0, 4, 12 and 24 of therapy.RESULTS: Only IL28 B rs12980275 was associated with treatment response in the Chinese Han population. Patients carrying AG/GG genotypes had a reduced rapid viral response compared with patients carrying the AA genotype(additive model: adjusted OR = 0.43, 95%CI: 0.24-0.75). It took less time for patients with the AA genotype to achieve a viral load 500 copies/m L(logrank test, P = 0.004). In addition, the protective effect of genotype AA was independent of baseline viral load. HCV genotype, and baseline white blood cell count, α-fetoprotein and viral load might also help predict treatment response. The area under the receiveroperating characteristic curve was 0.726. CONCLUSION: IL28 B rs12980275 AA genotype is a strong predictor of positive response to IFN therapy in Chinese Han patients with hepatitis C.     

Relationship between interleukin 18 polymorphisms and susceptibility to chronic hepatitis B virus infection

AIM:To identify the relationship between the tagging single nucleotide polymorphism sites(tagSNPs)of the Interleukin-18(IL-18)gene and genetic susceptibility to chronic hepatitis B virus infection in Chinese patients.METHODS:Five hundred and one cases of chronic hep-atitis B virus(HBV)infection and 301 HBV natural clearance controls were studied.Two tagSNPs in the IL-18 gene(rs1946518A/C and rs574424C/G)were genotyped by the Multiplex Snapshot technique.The genotype and allele frequencies were calculated and analyzed.RESULTS:In the genotypes of rs1946518,the AA type was present at a higher frequency in the patients compared to those in the controls.Odds ratio(OR)of theAA genotype for the comparison with that of the AC and the CC genotype was 1.537(95%confidence intervals(CI):1.116-2.218,P=0.009<0.025).In pheno-types,the allele C at rs1946518 was of a significantly lower frequency in the patients with chronic hepatitis B than that in the controls(P=0.017<0.025).OR of the allele A for the comparison with that of the allele C was 1.279(95%CI:1.045-1.567).As for the rs574424 genotypes,no significant difference in this genotype distribution or in this allele frequency between the patients and the control subjects was observed.No significant difference in the haplotype frequencies between the patients with chronic hepatitis B and HBV natural clearance individuals was displayed.CONCLUSION:The data suggest that genotype AA and the allele A of the IL-18 at position rs1946518 are closely associated with the resistance to chronic hepatitis B and may be the dangerous gene.However,no statistical association was found between polymorphisms of rs574424 for IL-18 and hepatitis B.     

贵州省地方性氟中毒地区人群GSTP1基因Ile105Val位点多态性分析

Objective To investigate plasma glutathione S-transferase(GSTs) activity and GSTP1 gene Ile105Val polymorphism in Bijie City, Guizhou Province, a coal-burning fluorosis endemic area. Methods One hundred and sixty villagers from Yachi Twon using non-improved cooking stoves were selected as the non-intervened group in Bijie City, Guizhou Province where coal-burning fluorosis was prevailing; 153 villagers as the intervented group were chosen from Changchun Twon, where cooking stoves were improved; 151 villagers were served as the control group from Baiyunshan Twon, Changshun County without endemic fluorosis. The activity of GSTs was tested by colorimetric analysis with spectrophotometer. The genotype of the GSTP1 gene Ile105Val polymorphism, presenting as either homozygous wild-type (AA), or heterozygous mutation type (AG), or homozygous mutation type (GG), was detected through the PCR-RFLP procedure. Results The activity of GSTs in plasma of non-intervened group [(12.44±4.97) kU/L]was significantly lower than that of intervened group (P < 0.05), and that of intervened group[(20.78±6.20)kU/L]was significantly lower than that of control group[(24.30±6.27)kU/L, P< 0.05]. The difference of the enzyme activity of three groups were statistically significant (F = 51.71, P < 0.05), but this enzyme activity did not vary significantly in each sex of each grnup(P > 0.05). Compared intervened group [AA:67.3%(103/153), AG:29.4%(45/153),GG:3.3%(5/153)]and non-intervened group[AA:66.9%(107/160), AG:30%(48/160), GG:3.1%(5/160)]with control group[AA:74.8%(113/151), AG:25.2%(38/151), GG:0 (0/151)], the Ile105Val polymorphism site of GSTP1 gene had significant difference(χ2= 6.04,6.07, both P< 0.05), but not significant between intervened and non-intervened groups(χ2 = 0.02, P>0.05). Conclusions Fluorosis can decrease the activity of GSTs and introduce the GSTP1 gene Ile105Val polymorphism, intervention with the fluorine intake will improve the effect of fluoride on the body.     

A common missense single nucleotide polymorphism in the E-selectin gene is significantly associated with essential hypertension in the Han population but only weakly associated in the Uygur population

Experimental and clinical observations suggest that E-selectin could have an important role in essential hypertension (EH), but the relationship between common E-selectin variants and EH has not been extensively studied in the Chinese population. In this study, we explored the association between two common variants in the E-selectin gene (rs5361A/C and rs5355C/T) and EH in the Uygur, Kazakh and Han populations in the Xinjiang area. A case-control study was conducted to explore the association between these two single-nucleotide polymorphisms and EH in a large sample size, including 941 EH subjects (309 Uygur, 264 Kazakh and 368 Han individuals) and 924 control subjects (300 Uygur, 275 Kazakh and 349 Han individuals). Univariate analysis showed that the rs5361 A/C polymorphism was significantly associated with EH in the Uygur (P=0.002) and Han (P=3.6 × 10(-7)) populations. The CC genotype of this SNP was present only in patients with EH in all of the three nationalities studied. Han individuals who carry the CC genotype of rs5361 were more susceptible to EH, according to the dominant models (P=1.13 × 10(-4), odds ratio=3.812, 95% confidence interval: 1.685-7.792), but there was no association of genotype with EH for the other ethnicities. No significant difference in rs5355 C/T polymorphism rate was found between the EH and control groups. Our results indicate that the common variant rs5361 is strongly associated with EH in Han individuals and weakly associated in Uygur individuals. The CC genotype of rs5361 might be an independent risk factor for EH among Uygur, Kazakh and Han individuals in the Xinjiang area.     

前列腺六次跨膜蛋白2基因变异与维吾尔族人群代谢指标及肿瘤坏死因子的关系

 目的 探讨前列腺六次跨膜蛋白2(STAMP2)基因功能区变异与新疆维吾尔族人群代谢指标及TNFα的关系。方法 采用以流行病学调查为基础的病例研究,选取维吾尔族个体894例,以TNFα水平分组:高水平组(TNFα≥7.95 μg/L)313例,中水平组(TNFα>5.34~<7.95 μg/L)268例,低水平组(TNFα≤5.34 μg/L)313例。首先在小样本代谢综合征患者中测序筛查STAMP2基因的变异位点,采用TaqMan-PCR方法在大样本人群中进行基因型鉴定及关联研究。结果 在STAMP2基因功能区选取3个代表性变异位点(rs8122、rs1981529和rs34741656),rs8122和 rs1981529的基因型及等位基因分布在不同TNFα水平3组间差异有统计学意义(P<0.05),rs34741656的基因型及等位基因分布在3组间差异无统计学意义(P>0.05)。方差分析发现rs1981529多态AA基因型与AG基因型间的TNFα水平差异有统计学意义[(2.77±0.33) μg/L比(2.83±0.31) μg/L,P<0.05], STAMP2不同基因型间的TC、HDL-C、LDL-C、TG水平差异无统计学意义(P>0.05)。结论STAMP2基因变异与新疆维吾尔族人群TNFα相关。         

神经前体细胞表达发育调控样蛋白4基因多态性与哈萨克族高血压病的关联研究

目的 研究神经前体细胞表达发育调控样蛋白4基因(NEDD4L)变异与哈萨克族高血压病的相关性.方法 采取以人群为基础的横断面病例-对照研究方法 .采用TaqMan PCR技术对rs4149601多态性在哈萨克族自然人群中(883例;男性375例,女性508例;高血压383例,对照500例)进行分型;分析该多态性与哈萨克族高血压病的相关性;然后联合分析rs4149601与既往采用直接测序法在本人群中发现的NEDD4L基因3个代表性变异位点(296921-296923delTTG,rs2288774和rs2288775)组成的单体型与哈萨克族高血压病的相关性.结果 (1)rs4149601多态性的基因型、等位基因的分布符合Hardy-Weinberg平衡,3个代表性多态位点与rs4149601多态性间未发现有意义的连锁不平衡(r2＜0.8＝;(2)rs4149601多态性的基因型、等位基因在高血压组、对照组分布差异无统计学意义;(3)在总体、男性中,rs4149601,296921-3delTTG,rs2288774和rs2288775四个多态位点组成的单体型在高血压组、血压正常组分布差异无统计学意义;在女性中,D-C-G-G(296921-3delTTG/rs2288774/rs2288775/rs4149601)单体型在高血压组的频率高于血压正常组,且差异有统计学意义(P=0.026).结论 rs4149601多态性与哈萨克族高血压病不相关;D-C-G-G(296921-3delTTG/rs2288774/rs2288775/rs4149601)单体型可能是新疆哈萨克族人高血压病的易感因素.     

STAMP2基因多态性与新疆维吾尔族男性原发性高血压相关性研究

目的:研究STAMP2基因多态性与新疆维吾尔族男性原发性高血压(EH)相关性.方法:采用以流行病学调查为基础的病例-对照研究,选取291例维吾尔族男性EH患者和445例男性正常血压者作为研究对象,首先选取STAMP2基因功能区的变异位点,选取代表性变异位点应用TaqMan-PCR在大样本人群中进行基因型鉴定及病例-对照...     

MK2基因与新疆维吾尔族女性三酰甘油的关联

目的:探讨MK2基因多态性与新疆和田地区维吾尔族女性三酰甘油（TG）的相关性。方法: 采用整群随机抽样方法抽取590个维吾尔族女性作为研究对象,检测其血脂水平以及肿瘤坏死因子-α（TNF-α）,并在48例维吾尔族血脂异常人群中测序筛查MK2基因功能区的变异位点,选取代表性变异位点,应用TaqMan-PCR在大样本人群中进行基因型鉴定及病例-对照研究。结果: MK2基因rs44890位点CC、CT、TT 3种基因型及C、T等位基因在TG正常组、TG边缘异常组、TG升高组分布频率差异具有统计学意义（P=0.023和0.004）;rs44890的不同基因型间TG差异无统计学意义,但有逐渐减少的趋势（CC>CT>TT）,同时还发现TNF-α在3种基因型间有逐渐减小的趋势（CC>CT>TT）,但差异无统计学意义;显性模型中,rs44890位点CT+TT基因型与TT基因型TG差异具有统计学意义（CC>CT+TT,P=0.021）。维吾尔族女性人群中rs45514798不同基因型间TG水平差异均无统计学意义。结论: MK2基因rs45514798位点与新疆维吾尔族女性TG不相关,rs44890位点与维吾尔族女性TG的关系有待进一步研究。     

Genetic Polymorphism of KCNH2 Confers Predisposition of Acquired Atrial Fibrillation in Chinese

Introduction: Nonfamiliar atrial fibrillation (AF) is usually associated with acquired structural heart disease, including valvular heart disease, coronary artery disease, and hypertension. Suggestive evidence indicates that these forms of acquired AF are more likely to occur in individuals with a genetic predisposition. We investigated the effect of the potassium channel voltage-gated subfamily member 2 ( KCNH2 ) gene on the prevalence of acquired AF in a Chinese population.
Methods: In a pair-matched, hospital-based case control study (297 vs 297) conducted in Chinese Hans, we investigated 4 tagging single nucleotide polymorphisms (tSNPs), rs1805120, rs1036145, rs3807375, and rs2968857 in the KCNH2 gene, and determined their association with AF acquired from structural heart diseases.
Results: We did not observe the association of rs1036145, rs3807375, and rs2968857 with AF. However, we determined that the tSNP, rs1805120, in exon 6 confers the risk of AF in Chinese Hans. Both genotype and allele frequencies of rs1805120 were distributed differently in cases and controls (P = 0.0289 and P = 0.0172, respectively). The most significant association was observed under a recessive model for the minor GG genotype with a 1.45-fold risk of developing AF (95% confidence interval 1.09–1.93, P = 0.012). The significance remained after controlling for the covariates of age, smoking, BMI, hypertension, and diabetes.
Conclusion: We report a new genetic variation (rs1805120) in the KCNH2 gene that predisposes Chinese Han individuals to the risk of acquired AF. Further genetic and functional studies are required to identify the etiological variants in linkage disequilibrium with this polymorphism.     

IRGM和ATG16L1基因多态性与中国汉族人群克罗恩病的相关性

目的分析IRGM和ATG16L1基因多态性与中国汉族人群克罗恩病(crohn’s disease,CD)发病的相关性。方法选取中国汉族CD患者和健康对照者各318例纳入研究,采用聚合酶链式反应和直接测序方法检测其IRGM和ATG16L1基因的基因型,比较两组间基因型和等位基因频率。结果 CD组和正常对照组IRGM基因rs13361189位点、ATG16L1基因rs2241880位点基因型和基因频率分布均符合Hardy-Weinberg遗传平衡定律,两组间2种基因相应的SNP位点的基因型和等位基因频率差异均无统计学意义(P>0.05)。结论虽然IRGM和ATG16L1基因的遗传变异与西方白种人CD的易感性相关,但是IRGM和ATG16L1基因多态性却与中国汉族人CD无明显相关性。     

血清淀粉样蛋白A1基因多态性对汉族人群颈动脉内中膜厚度的影响

目的 探讨血清淀粉样蛋白A1(SAA1)基因多态性对颈动脉内中膜厚度(IMT)的影响.方法资料来源于2007至2010年"新疆维吾尔自治区不同民族心血管疾病危险因素调查研究"数据,人选其中健康汉族人群449例,采用限制性片段长度多态性(RFLP)方法对SAA1基因rs2229338和rs12218进行分型.彩色超声检测颈总动脉干部内中膜厚度(CC-IMT)和膨大部内中膜厚度(CB-IMT),分析不同基因型之间颈动脉IMT的差异.结果 (1)rs2229338和rs12218存在强连锁不平衡(D'=0.89).(2)SAA1基因rs2229338突变型(GG+AG)与野生型(AA)的CC-IMT和CB-IMT值差异均无统计学意义.(3)SAA1基因rs12218突变型(CC+CT)CC-IMT值大于野生型(TT)[(0.081±0.071)cm比(0.068±0.019)cm,P=0.01],在校正年龄、性别、血压、腰围、肌酐和高密度脂蛋白胆固醇的影响后,差异仍具有统计学意义(P=0.04);rs12218突变型(CC+CT)与野生型(TT)的CB-IMT值差异无统计学意义[(0.085±0.038)cm比(0.081±0.052)cm,P=0.36].结论在新疆维吾尔自治区汉族人群,SAA1基因多态性和颈动脉IMT存在关联,rs12218突变型基因可能会增加颈动脉IMT.

Abstract：

Objective To explore the association between genetic polymorphism of serum amyloid protein A1 (SAA1) with carotid intima media thickness in a healthy Han Chinese population of Xinjiang. Methods A total of 449 healthy Han Chinese participating the cardiovascular risk survey between June 2007 and September 2009 were included, the genotypes of the SAA1 were detected by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The mean IMT of the right and left common carotid arteries were measured by B-mode ultrasonography. Results (1) There was strong linkage disequilibrium between rs12218 and rs2229338 (D'=0. 89). (2) The carotid common IMT (CC-IMT) and the carotid bulb IMT (CB-IMT) were similar between the AA genotype (wild genotype) and the GGFAG genotype (mutational genotype) in rs2229338 of SAA1 gene. (3) CC-IMT[(0.081 ±0.071)cm vs (0.068 ±0. 019 ) cm, P = 0. 01] was significantly thicker in CC + CT genotype ( mutational genotype) group than in TT genotype (wild genotype) of rs12218 group and the difference remains significant after adjustment for age,gender,blood pressure, waist circumference, creatinine and high density lipoprotein cholesferoL CB-IMT [(0.085±0. 038)cm vs. (0.081 ± 0. 052) cm,P =0. 36] was similar between CC +CT genotype and TT genotype of rs12218 groups. Conclusion Our results suggested that the genetic polymorphism of SAA1 might be linked with IMT and rs12218 mutation could serve as a promoting factor for IMT in Han Chinese people.     

Genetic variation in the ASIC3 gene influences blood pressure levels in Taiwanese

BACKGROUND: The acid-sensing ion channel 3 (ASIC3) is a ligand-gated cation channel activated by extracellular protons, and is associated with an exercise-induced pressor reflex and possibly autonomic imbalance. METHODS: To test the statistical association between genetic polymorphisms of the ASIC3 gene and blood pressure (BP) variations in Taiwanese, 551 unrelated individuals (286 men and 265 women) were recruited from a routine health examination. The participants had no prior history of cardiovascular disease or medication use for hypertension. RESULTS: Six ASIC3 gene polymorphisms were genotyped; three were polymorphic, and only the rs2288646 polymorphism was associated with variations in BP among participants. Significantly higher systolic, diastolic, and mean BP were observed in participants carrying the rs2288646-A allele (P=0.034, 0.023, and 0.010, respectively). Significantly higher frequencies of the rs2288646-A-containing genotype were observed in normotensive, prehypertensive, and hypertensive subgroups (P for trend=0.026); and in those with higher systolic and diastolic BPs (P for trend=0.005 and P for trend=0.002, respectively). The association between the rs2288646-A allele and BP persisted even after adjustment for age, sex, BMI, and other metabolic factors. When a second independent group of 403 individuals was combined with the first group of 551 (n=954), a significantly higher frequency of the rs2288646-A-containing genotype was observed in participants with hypertension (9.7 vs. 4.0%, P=0.003). CONCLUSION: Our data showed an independent association between an ASIC3 genetic polymorphism and BP variations in Taiwanese. These results suggest that the ASIC3 may be involved in BP regulation.     

PPAP2B基因单核苷酸多态性与冠心病的关联研究

目的研究PPAP2B基因单核苷酸多态性(SNP)位点与中国汉族人冠心病(CHD)发病的相关性。方法共收集525例CHD患者和650例正常对照(NC),采用病例-对照关联研究的方法 ,选取PPAP2B基因的4个标签SNP,包括已有报道的rs17114036位点,采用单碱基延伸法(SNaPshot)进行基因分型,并分析其与冠心病的相关性。结果 PPAP2B基因4个标签SNP:rs6588635、rs17114036、rs2404715和rs17407790的基因型分布均符合Hardy-Weinberg平衡(P>0.05)。其等位基因频率在CHD组与NC组间有显著差异(rs6588635P=0.00167、rs17114036P=0.00581、rs2404715P=0.0174、rs17407790P=0.00124)。通过单倍体型分析发现,这4个SNP位点处于同一个连锁不平衡区域,其中风险单倍体型TACC可以增加冠心病易感性0.73倍(P=0.0012),而保护型的单倍体型CGTT可降低冠心病的患病风险47%(P=0.0025)。结论 PPAP2B基因SNP位点与冠心病发病显著相关,其危险等位基因可增加冠心病的易感性。