GALNT2 rs4846914多态性位点在中国汉族人群分布及其对血脂的影响

目的 研究多肽N-乙酰半乳糖胺基转移酶2(N-acetylgalactosaminyltransferase 2,GALNT2)基因rs4846914位点在中国汉族人群中的分布频率,分析该位点对血脂水平和血脂异常的影响.方法 采用横断面调查方法,收集2397例(其中男性1511例,女性886例)汉族人群样本.采用MALDI-TOF MS技术检测rs4846914位点基因分型,采用多重线性回归法分析基因型对4项血脂指标影响程度的大小,二分类Logistic回归法分析基因型对血脂异常发病风险的大小,以P＜0.05为有统计学意义.结果 GALNT2 rs4846914位点A等位基因在中国汉族人群中的频率为20.4％.AA基因型人群的高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)水平显著高于GG基因型(P=0.034),女性人群AA基因型的总胆固醇(total cholesterol,TC)水平也显著高于GG型(P=0.019).在男性人群,AA基因型的低HDL-C血症发病风险是GG基因型的0.478倍.(P=0.045,OR=0.478,95％ CI:0.233-0.983).结论 中国汉族人群rs4846914位点以G等位基因为主,明显不同于西方人群以A等位基因为主的特点.中国汉族人群中,该位点AA基因型可增加血浆HDL-C水平,并减少男性低HDL-C血症发生.     

1p13.3 rs599839单核苷酸多态性与早发冠状动脉粥样硬化性心脏病的关联研究

目的 探讨中国汉族人群染色体1p13.3 rs599839基因多态性与早发冠状动脉粥样硬化性心脏病(简称早发冠心病)的相关性.方法 用聚合酶链反应-限制性片段长度多态性技术分析303例经冠状动脉冠脉造影确诊的早发冠心病患者rs599839基因多态性,以同期冠脉造影阴性、排除冠心病诊断的312名受试者为财照组,比较两组间rs599839基因多态性频率分布差异.结果 早发冠心病组与对照组中均检出AA、AG基因型,GG基因型末检出.G等佗基因频率在早发冠心病组和对照组中分别为5.0%、9.1%,差异有统计学意义(P=0.004),使用Logistic回归分析排除吸烟、高血压、糖尿病等因素的影响后,两组G等位基因频率差异仍有统计学意义(P＜0.05).两组中G等位幕因携带者(AG型)低密度脂蛋白胆固醇(low density lipoprotein-cholesterol,LDL-C)水平均低于AA纯合子.结论 中国汉族人群染色体1p13.3 rs599839基因多态性可能与早发冠心病发病相关;rs599839基因多态性可能与血清LDL-C浓度差异相关;rs599839基因多态性与冠脉狭窄程度无关.     

新疆维吾尔族、汉族健康人群血清淀粉样蛋白A1基因多态性分布特征

目的 探讨血清淀粉样蛋白A1(serum amyloid protein A1,SAA1)基因标签单核苷酸多态(tagging single nucleotide polymorphism,tagSNP)rs2229338和rs12218在新疆维吾尔族和汉族健康人群中的分布特征.方法 入选新疆地区维吾尔族(n=316)和汉族(n=362)健康人群,采用限制性片段长度多态性的方法进行基因分型.结果 (1)rs2229338三种基因型在维吾尔族人群中的分布频率分别为:AA型76.6%,AG型23.4%,GG型0;在汉族人群中的分布频率分别为:AA型91.7%,AG型7.7%,GG型0.6%.两组基因型分布差异有统计学意义(P＜0.01);(2)rs12218三种基因型在维吾尔族人群中的分布频率分别为:CC型10.1%,CT型47.5%,TT型42.4%;在汉族人群中的分布频率分别为:CC型3.3%,CT型34.3%,TT型62.4%.两组基因型分布差异有统计学意义(P＜0.01);(3)rs12216和rs2229338共构建4个单倍型,其中A-C和G-T单倍型在维吾族中的分布明显高于汉族(P＜0.01),A-T单倍型在汉族中的分布明显高于维吾尔族(P＜0.01).结论 SAA1基因标签SNP在新疆汉族和维吾尔族健康人群中的分布具有明显的差异,维族人群突变频率可能高于汉族人群.     

云南地区汉族人群PSMB8、PSMB9及TAP2基因多态性与类风湿关节炎的关联研究

目的 研究云南汉族人群中PSMB8、PSMB9及TAP2基因多态性与类风湿关节炎(rheumatoid arthritis,RA)的相关性.方法 应用聚合酶链反应-限制性片段长度多态性法对177例RA患者及288名健康对照PSMB8基因的rs2071543、rs55745125、rs138635403位点和PSMB9基因的rs17587多态性位点进行基因分型,应用多聚酶链反应扩增阻碍系统法对TAP2基因的rs2228396多态性位点进行基因分型.计算基因型及等位基因频率.采用Epi Info 7软件计算上述多态位点在RA组及正常对照组之间的比值比(OR值).结果 rs138635403及rs17587位点的等位基因及基因型频率在RA组和对照组间差异有统计学意义(P＜0.05),其中RA组rs17587的GG基因型频率(0.672)高于对照组(0.524)(OR=1.862,95％CI:1.261～2.749).结论 云南汉族人群PSMB9基因的rs17587位点多态性与RA存在关联.     

中国广西人群S100B基因rs1051169G/C和rs9984765T/C的多态性

目的探讨中国广西人群S100B基因rs1051169 G/C和rs9984765 T/C位点遗传多态性的分布特征,并比较其与不同种族和地区人群的分布差异。方法采用单碱基延伸技术(SBE-PCR)和DNA测序法对398例广西体检者的S100B基因rs1051169 G/C和rs9984765 T/C位点进行基因分型,统计学分析其基因多态性的分布特征,并与国际人类基因组单体型图计划(Hap Map)数据库公布的Hap Map-具有北欧和西欧血统的犹他州人群(CEU)、Hap Map-非洲尼日利亚伊巴丹的约鲁巴人(YRI)、Hap Map-日本东京人群(JPT)和Hap Map-中国北京汉族人群(HCB) 4个人群的单核苷酸多态性(SNP)分型数据进行比较。结果广西人群S100B基因rs1051169 G/C位点存在GG、CG和CC基因型,其频率分别为41. 2%、44. 7%和14. 1%,G和C等位基因频率分别为63. 6%和36. 4%。rs9984765 T/C位点存在TT、CT和CC基因型,其频率分别为47. 7%、44. 5%和7. 8%,T和C等位基因频率分别为70. 0%和30. 0%。rs1051169 G/C和rs9984765 T/C位点的基因型和等位基因的分布频率差异均无统计学意义(P0. 05)。rs1051169 G/C基因型和等位基因频率与Hap Map-CEU、Hap Map-YRI和Hap Map-JPT比较差异均有统计学意义(P0. 01),与Hap Map-HCB比较,等位基因频率差异有统计学意义(P0. 05),基因型频率差异无统计学意义(P0. 05)。rs9984765 T/C位点的基因型和等位基因频率与Hap Map-YRI、Hap Map-JPT和Hap Map-HCB比较差异均有统计学意义(P0. 05),与Hap Map-CEU比较差异无统计学意义(P 0. 05)。结论广西人群S100B基因rs1051169 G/C和rs9984765 T/C位点存在多态性,且其多态性与不同种族和地区人群比较存在差异。     

TLR5rs5744168基因多态性与广西壮、汉族人系统性红斑狼疮的相关性研究

目的:探讨TLR5rs5744168基因单核苷酸多态性与广西壮、汉族系统性红斑狼疮易感性的相关性以及种族间差异,初步阐明其在壮、汉族SLE发生发展中的作用.方法:采用聚合酶链反应PCR技术和直接测序的方法对33例壮族、44例汉族系统性红斑狼疮患者和72名壮、汉族健康对照者的TLR5rs5744168C/T基因多态性进行分析,比较组间基因型和等位基因频率的差异,并与主要临床指标进行相关性分析.结果:(1)广西地区壮、汉族SLE的TLR5 rs5744168的TT基因型均缺失;CC基因型频率在各组中均在90.0％～100.0％之间.(2)广西壮族SLE患者TLR5基因rs5744168 CC、CT基因型频率分别是0.939、0.061,汉族SLE患者相应基因型频率分别是0.977、0.023,与相应民族正常对照组间以及壮、汉族SLE间差异均无统计学意义(分别x2 =2.001 x2=2.235和x2 =0.723;均P＞0.05);壮族SLE患者的TLR5rs5744168 C、T等位基因频率分别是0.970、0.030,汉族SLE相应的C、T等位基因频率分别是0.989、0.011,与相应民族正常对照组间以及壮、汉族SLE间差异均无统计学意义(分别x2=1.970、x2 =2.166和x2=0.708;均P＞0.05).(3)TLR5rs5744168 CC、CT基因型及C、T等位基因与广西壮汉族SLE患者ds-DNA、ANA、肾损害临床表现和实验室检查均无相关性(均P＞0.05).结论:TLR5rs5744168基因多态性与广西壮、汉族SLE的易感性以及ds-DNA、ANA、肾损害临床实验室主要指标均无明显相关性,壮、汉族间亦不存在明显民族差异性.     

多囊卵巢综合征患者FEM1A基因的多态性研究

目的 通过分析多囊卵巢综合征(polycystic ovary syndrome,PCOS)患者FEMlA基因单核苷酸多态性(single nueleotide polymorhisms,SNPs),初步探讨FEMlA基因多态性与PCOS的关系.方法 采用SNPs直接DNA测序法对120例PCOS患者和155名健康志愿者FEMlA基因的rs12460989和rs8111933位点进行分型,同时分析其与高雄激素血症、胰岛素抵抗(insulin resistance,IR)的关系.结果 中国汉族人群FEMlA基因rs12460989检测到TT、TG和GG等3种基因型,rs8111933检测到GG、GC和CC等3种基因型.与对照组相比,PCOS组rs12460989和rs8111933等位基因分布的差异均有统计学意义(X2=33.302,P＜0.01;X2=11.252,P＜0.01).多因素非条件Logistic回归分析显示,rs12460989 TG+GG基因型和rs8111933 GC+CC基因型人选高雄激素血症风险因素的主效应模型,rs8111933 GC+CC基因型入选IR风险因素的主效应模型.结论 FEMIA基因rs12460989、rs8111933多态性与PCOS的发病风险存在关联.两者可能是高雄激素血症潜在的风险因素,且rs8111933多态性可能是IR潜在的风险因素.     

CDKAL1基因rs4712523多态性与内蒙古地区汉族人群2型糖尿病相关

目的 研究内蒙古地区汉族人群CDKAL1基因rs4712523单核苷酸多态性(SNP)的等位基因和基因型频率分布与2型糖尿病(T2DM)的相关性.方法 采用等位基因特异性聚合酶链式反应(AS-PCR),对382例内蒙古地区汉族人(其中T2DM组192例,对照组190例)rs4712523进行基因分型.结果 T2DM组中rs4712523的G等位基因频率和GG基因型频率分别为47.4％和6.3％,均显著高于对照组的35.3％和3.2％(P＜0.05).G等位基因携带者患T2DM的风险是A等位基因的1.654倍(OR=1.654,95％ CI=1.237-2.212).结论 CDKAL1基因rs4712523多态性位点的G等位基因可能是内蒙古地区汉族人T2 DM的易感基因之一.     

Vitamin D receptor ApaI (rs7975232), BsmI (rs1544410), Fok1 (rs2228570), and TaqI (rs731236) gene polymorphisms and susceptibility to pulmonary tuberculosis in an Iranian population: A systematic review and meta-analysis

Polymorphisms of vitamin D receptors (VDRs), ApaI, BsmI, FokI, and TaqI might affect susceptibility to tuberculosis (TB). In this systematic review and meta-analysis, all published articles which investigated the effects of these polymorphisms on the risk of TB in the Iranian population were retrieved.PubMed and Scopus were searched with no date or language restrictions. In this meta-analysis, the Comprehensive Meta-Analysis (CMA) version 2.0 and random effects model were applied. The association of polymorphisms with TB risk was assessed by measuring the odds ratio (ORs) at 95% CI. Heterogeneity was investigated based on Cochran Q-test and I2-index statistics. The significance level was set at 0.05. Also, Egger's regression intercept was determined to measure publication bias.A total of six articles on Iranian populations were included. TaqI (5/6 included studies) showed a significant association with the increased risk of TB based on ORs (allele comparison: 1.57 (1.0, 2.3), p-value: 0.02; additive model of tt/TT: 1.57 (0.9, 2.5), p-value: 0.05; recessive model (tt/Tt + TT): 1.99 (1.2, 3.2), p-value: 0.00; dominant model (tt + Tt/TT): 1.98 (1.1, 3.5), p-value: 0.01). BsmI showed a significant positive effect on TB risk only in its dominant genotype (bb + bB/BB) (1.44 (1.0, 1.9); p-value: 0.02). FokI and ApaI did not show any significant effects on TB development in Iranian populations. Findings showed the significant effect of TaqI polymorphism in all genetic models and the dominant model of BsmI on the increased risk of TB. However, the effects of TaqI and BsmI should be further investigated in a larger sample size.     

INSIG2 gene rs7566605 polymorphism is associated with severe obesity in Japanese

The single nucleotide polymorphism (SNP) rs7566605 in the upstream region of the insulin-induced gene 2 (INSIG2) is associated with the obesity phenotype in many Caucasian populations. In Japanese, this association with the obesity phenotype is not clear. To investigate the relationship between rs7566605 and obesity in Japanese, we genotyped rs7566605 from severely obese subjects [n = 908, body mass index (BMI) >/= 30 kg/m(2)] and normal-weight control subjects (n = 1495, BMI < 25 kg/m(2)). A case-control association analysis revealed that rs7566605 was significantly associated with obesity in Japanese. The P value in the minor allele recessive mode was 0.00020, and the odds ratio (OR) adjusted for gender and age was 1.61 [95% confidential interval (CI) = 1.24-2.09]. Obesity-associated phenotypes, which included the level of BMI, plasma glucose, hemoglobin A1c, total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and blood pressure, were not associated with the rs7566605 genotype. Thus, rs7566605 in the upstream region of the INSIG2 gene was found to be associated with obesity, i.e., severe obesity, in Japanese.     

Effects of rs6234/rs6235 and rs6232/rs6234/rs6235 PCSK1 single-nucleotide polymorphism clusters on proprotein convertase 1/3 biosynthesis and activity

Background

Proprotein convertase 1/3 (PC1/3) is one of the endoproteases initiating the proteolytic activation of prohormones and proneuropeptides in the secretory pathway. It is produced as a zymogen that is subsequently modified by activity-determining cleavages at the amino and the carboxyl termini. In human, it is encoded by the PCSK1 locus on chromosome 5. Spontaneous inactivating mutations in its gene have been linked to obesity. Minor alleles of the common non-synonymous single-nucleotide polymorphisms (SNPs) rs6232 (T > C, N221D), rs6234 (G > C, Q665E) and rs6235 (C > G, S690T) have been associated with increased risk of obesity. We have shown that the variations associated with these SNPs are linked on minor PCSK1 alleles.

Goal

In this study, we examined the impact of amino acid substitutions specified by the minor PCSK1 alleles on PC1/3 biosynthesis and prohormone processing activity in cultured cells.

Methods

The common and variant isoforms of PC1/3 were expressed in transfected rat pituitary GH4C1 cells with or without proopiomelanocortin (POMC) as a substrate. Secreted PC1/3- or POMC-related proteins and peptides were analyzed by immunoblotting and immunoprecipitation.

Results

When expressed in GH4C1 cells, the triple-variant PC1/3 underwent significantly more proteolytic processing at the amino and carboxyl termini than the common and double-variant isoforms. However, there was no detectable difference among these isoforms in their ability to process POMC in the transfected cells.

Conclusions

Since truncation of PC1/3 in its C-terminal region reportedly renders the enzyme unstable, we speculate that the accentuated processing of the triple variant in this region may, in vivo, create a subtle deficit of PC1/3 enzymatic activity in endocrine and neuroendocrine cells, causing impaired processing of prohormones and proneuropeptides to their bioactive forms.     

心肌钾离子通道β亚单位基因rs1805127多态性与新疆维吾尔族心房颤动的相关性

目的 研究心肌钾离子通道β亚单位基因(KCNE1) rs1805127多态性与新疆维吾尔族心房颤动(房颤)的相关性.方法 应用聚合酶链反应-限制性片段长度多态性方法,对303例房颤患者和328名健康受试者(对照组)KCNE1基因rs1805127多态位点进行检测,采用非条件多元Logistic回归分析综合评价各因素与房颤的关系.结果 KCNE1基因rs1805127位点AA、AG、GG基因型频率在房颤组分别为0.092(28/303)、0.386(117/303)和0.522(158/303),在对照组分别为0.122(40/328)、0.485(159/328)和0.393(129/328),2组基因型分布差异具有统计学意义(x2=10.465,P=0.005),且房颤组G等位基因频率(0.715)明显高于对照组(0.636)(x2=8.907,P=0.003);Logistic回归分析结果显示KCNE1基因多态性仍是维吾尔族房颤发生的重要危险因素,基因型GG的OR值为1.55,95%CI:0.73～3.27.结论 KCNE1基因rs1805127多态性可增加新疆维吾尔族房颤的发生风险.     

Association of Nod‐like receptor protein‐1 (rs2670660) and Toll‐like receptor‐4 (rs4986790) with non‐segmental vitiligo: A case–control study in South Indian population

Non‐segmental vitiligo (NSV) is an autoimmune skin disease. Genetics plays a predominant part in disease pathogenesis. Nucleotide‐binding and oligomerization domain (NOD)‐like receptors and pyrin‐containing protein (NLRP) and Toll‐like receptors (TLR) are pattern recognition receptors in mediating innate immunity. They participate in presenting pathogens and mediating the immune responses. NLRP and TLRs are involved in mediating immune response in various dermatological diseases. Understanding the influence of genetic polymorphisms of NLRP and TLRs associated with immune homeostasis might help us to understand the complex etiopathogenesis of NSV. Thus, we aimed to study the association of NLRP‐1 (rs2670660) and TLR‐4 (rs4986790) and the synergistic effects on disease spectrum, disease activity of NSV in South Indian population. This research was designed as a case–control genetic study with 264 patients and 264 controls. Genotyping of NLRP‐1 (rs2670660) and TLR‐4 (rs4986790) was performed by Taqman 5’ allele discrimination assay and ARMS‐PCR. Plasma levels of proteins were measured by enzyme‐linked immunosorbent assay (ELISA). A statistically significant difference was observed with the frequency of homozygous GG genotype of NLRP‐1 (rs2670660) (17.8% in cases vs. 5.3% in controls) (p < 0.0001; OR‐3.73; 95% CI‐1.94–7.14). Allele G was significantly frequent in 38% of the cases than in controls with 30% (p = 0.004; OR‐1.46; 95% CI‐1.13–1.89). Plasma NLRP‐1 level was significantly higher in patients compared to controls (p < 0.05). Amongst cases, the plasma NLRP‐1 levels did not show any difference with respect to their genotypes (p > 0.05). In TLR‐4 (rs4986790), no significant difference in the frequency of genotypes and allele between cases and controls (p = 0.80) was observed; nevertheless, plasma TLR‐4 was analogous between cases and controls (p > 0.05). Influence of genotype on plasma TLR‐4 showed no significant difference in TLR‐4 levels between GG and ancestral genotype AA, whilst heterozygous AG genotype showed a significant increase of TLR‐4 compared to AA and GG (p = 0.02) amongst NSV cases. The obtained results suggest that NLRP‐1 (rs2670660), and not TLR‐4 ((rs4986790), is associated with increased risk of NSV in South Indian population.     

Influence of the TNFSF4 rs1234315 polymorphism in the susceptibility to systemic lupus erythematosus and rheumatoid arthritis

ObjectivesThe tumour necrosis factor superfamily 4 (TNFSF4) is a candidate gene for autoimmune diseases. We investigated the relationship of this gene with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in a Chinese Guangxi population.MethodsA total of 294 patients with SLE, 210 with RA, and 282 healthy controls were genotyped for single nucleotide polymorphism (SNP) rs1234315 using the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). The potential functional effects of the SNP were predicted by in silico analysis.ResultsStatistically significant associations with SLE and RA were detected at rs1234315, both by allele analysis (odds ratio 1.47, 95% confidence interval 1.17–1.86, p = 0.001; odds ratio 1.49, 95% confidence interval 1.15–1.92, p = 0.002; respectively), and genotype analysis (p = 0.003 and p = 7.000 × 10⁻⁵, respectively). The Akaike’s information criterion (AIC) values indicated that the recessive model may serve as the best-fit model for the SNP for SLE and RA.ConclusionOur results provided support for TNFSF4 rsl234315 as a SLE and RA susceptibility locus in a Chinese Guangxi population.     

Lack of Association Between TESPA1 Gene Polymorphisms (rs1801876, rs2171497, rs4758994, and rs997173) and Ankylosing Spondylitis in a Chinese Population

We investigated whether TESPA1 gene polymorphisms were associated with increased risk of developing ankylosing spondylitis (AS). We also studied whether TESPA1 gene interacts with environmental factors. A total of 494 patients with AS and 478 matched healthy controls were genotyped for four SNPs (rs1801876, rs2171497, rs4758994, and rs997173) in the TESPA1 gene. We found no evidence of association between these SNPs and AS susceptibility, and between their haplotypes and the disease. But, patients with rs1801876 GA, GG, and AA genotypes had significantly different Bath Ankylosing Spondylitis Functional Index (BASFI) scores (p?=?0.023). There were significantly different visual analogue scale (VAS) night pain assessment scores (p?=?0.040) and BASFI scores (p?=?0.023) among different genotypes at rs2171497 locus. There were also significantly different chest expansion scores (p?=?0.042) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores (p?=?0.014) among different genotypes at rs997173 locus. For multiple testing, Bonferroni correction was performed. After Bonferroni correction, clinical characteristics of these three loci showed association between different genotype groups. These findings indicated that the TESPA1 gene is not involved in AS genetic predisposition in the Han Chinese population; however, it may play an important role in the clinical characteristics of AS.     

GDF5基因rs224331多态性与汉族青少年体格发育指标关联分析

目的探讨中国汉族青少年GDF5基因rs224331位点多态性与身高、体重和BMI的相关性。方法采集江苏省某技校1790名17～22岁青少年的身高、体重指标并计算BMI。采用Taqman探针real-timePCR方法检测GDF5基因rs224331位点的单核苷酸多态性,并分析该基因位点与男女生身高、体重和BMI的相关性。结果 97.9%（1754/1790名）基因分型成功,男生859名,女生895名。rs224331位点频率最高的基因型为AA（51.7%）,其次为AC（39.6%）,CC最少（8.7%）。rs224331的基因型分布与男生、女生的身高无显著关联（P分别为0.728和0.723）;rs224331不同基因型间的男生体重和BMI差异均有统计学意义（P均〈0.01）,男生AC基因型体重和BMI均显著高于AA基因型（P=0.002）,女生中未发现类似的相关性（P分别为0.713和0.921）。结论 GDF5基因rs224331位点多态性在本研究的汉族人群中与身高无明显关联,提示该多态性位点可能存在种族特异性。rs224331位点多态性与男生体重和BMI存在相关性。