KCTD15基因rs11084753位点多态性与石家庄市社区体检人群肥胖超重现状的相关性

目的探讨含钾通道四聚化结构域15(KCTD15)基因rs11084753位点多态性与石家庄市社区人群肥胖的相关性。方法应用2012~2013年河北省人民医院体检中心体检人群调查资料,对97 588例18岁以上人群的超重、肥胖现状及影响因素进行流行病学分析。应用直接测序法对其中4 500例人员(肥胖组人员3 500例、对照组人员1 000例)EDTA抗凝血KCTD15基因的多态性情况进行检测。结果体检人群中男性体重指数(BMI)(27.61±11.48)kg/m2,女性BMI(24.76±11.58)kg/m2;男性腰围(WC)(88.57±16.47)cm,女性WC(77.14±14.36)cm,女性BMI及WC随年龄的增加而增大。男性BMI以35~44岁为最高,WC以55~64岁为最高。超重、肥胖的现患率分别为41.97%和18.14%,男性(48.87%、22.10%)高于女性(33.84%、13.49%)(P<0.05)。基因多态性分析显示,肥胖人群KCTD15基因rs11084753位点GG及AG基因型明显高于对照组(P<0.05);Logistic回归分析显示,基因型是BMI的独立影响因素。结论石家庄市社区体检人群超重和肥胖发生率明显升高,这些人员肥胖超重与KCTD15基因rs11084753位点多态性有关。     

OCTN1/OCTN2基因多态性与中国汉族人群炎症性肠病相关性的初步研究

近年研究证实OCTN1/OCTN2基因单核苷酸多态性（SNP）与西方白种人群克罗恩病（CD）明显相关,其中OCTN1基因rs1050152位点和OCTN2基因rs2631367位点SNP与CD的相关性尤为显著.目的：初步探讨OCTN1基因rs1050152位点和OCTN2基因rs2631367位点基因多态性与中国汉族人群炎症性肠病（IBD）的相关性.方法：KR联合直接测序法检测45例CD患者、45例溃疡性结肠炎（UC）患者和50名正常对照者OCTN1基因rs1050152位点和OCTN2基因rs2631367位点的基因型,比较各组基因型和等位基因频率.结果：CD,UC和正常对照组间OCTN1基因rs1050152位点基因型和等位基因频率差异均无统计学意义（R〉0.05）;三组OCTN2基因rs2631367位点均未发现突变基因型.结论：OCTN1基因rs1050152位点和OCTN2基因rs2631367位点基因多态性与中国汉族人群IBD不相关.     

中国汉族人群NOD2、IRGM、ATG16L1和STAT4基因多态性与克罗恩病的相关性研究

背景：克罗恩病（CD）的病因和发病机制尚未完全阐明,近年国外研究发现NOD2、IRGM、ATG16L1、STAT4基因突变与CD相关。目的：分析NOD2、IRGM、ATG16L1、STAT4基因多态性与中国汉族人群CD发病的相关性。方法：连续纳入2007年1月～2010年1月苏州市立医院中国汉族CD患者66例,66名健康体检者作为正常对照,以PCR联合基因测序检测4种基因相应单核苷酸多态性（SNP）位点的基因型,分析各基因型和等位基因频率。结果：CD组和正常对照组NOD2基因rs2066842位点、IRGM基因rs13361189位点、ATG16L1基因rs2241880位点和STAT4基因rs7574865位点基因型和等位基因频率分布均符合Hardy-Weinberg遗传平衡定律,两组间4种基因相应SNP位点的基因型和等位基因频率差异均无统计学意义。结论：NOD2、IRGM、ATG16L1和STAT4基因多态性与中国汉族人群CD发病不相关。     

PKBα/Akt1基因多态性与2型糖尿病的相关性研究

目的 研究蛋白激酶B α亚型(PKBα,也称Akt1)基因单核苷酸多态性(SNP)与上海地区汉族人群2型糖尿病易感性的关系.方法 利用等位基因特异PCR技术对460例2型糖尿病患者及444名正常对照者(NC组)Akt1基因3个标签SNP位点rs2494743、rs2494738和rs3001371进行基因分型.结果 位点rs2494738和rs3001371的基因型分布在糖尿病组和NC组之间呈现显著性差异(均P＜0.01);rs2494738和rs3001371等位基因频率在2型糖尿病组和NC组的分布也呈现显著性差异(均P＜0.01);rs2494738的多态性与2型糖尿病发生风险呈等位基因计量效应关系.但rs2494743基因型和等位基因分布在NC组与2型糖尿病组中差异无统计学意义.单倍型分析结果显示3个单倍型频率在2型糖尿病组和NC组之间也存在显著差异(均P＜0.01).结论 在上海地区的汉族人群中,Akt1基因可能是2型糖尿病的易感基因之一;其SNP位点rs2494738和rs3001371变异可能与2型糖尿病发病相关.     

我国北方汉族人群甲状腺腺瘤相关基因单核苷酸多态性与2型糖尿病的关联研究

目的 评估甲状腺腺瘤相关基因（THADA）与中国北方汉族人群2型糖尿病（T2DM）的相关性。方法以1050例T2DM患者和1030名糖耐量正常者（NGT）为研究对象,采用病例一对照研究设计,对THADA基因区的5个单核苷酸多态性（SNPs）位点：rs13026309、rs13029250、rs13022691、rs4952986、rs6739828进行基因分型,通过Logistic回归、线性回归分析等位基因变异与T2DM及其相关性状的关联。结果女性NGT人群在相加遗传模式下调整年龄、性别和BMI后,rs4952986位点与FIns（P=0．0095）、HOMA—IR（P=0．0123）、HOMA-β（P=0．0089）相关。结论THADA基因的rs4952986位点在中国北方汉族女性人群中,与胰岛素抵抗、胰岛素分泌功能相关,所选的5个位点未发现与T2DM相关。     

2型糖尿病患者中血尿酸相关基因的基因间相互作用分析

目的 探讨T2DM患者中SUA与相关基因的关联及交互作用.方法 纳入1574例T2DM患者,采用基质辅助激光解吸电离飞行时间质谱技术对56个基因的86个SNP位点进行基因分型,运用PLINK软件进行关联分析及基因型交互作用分析.结果 在T2DM患者中ABCG2（rs2231142）、PKHD1（rs9395706）、PDGFB（rs2285094）、LPHN3 （rs6856526）及MC4R（rs17782313）基因的多态性与SUA水平相关（P＜0.05）.同时,有6组基因存在交互作用（P＜0.001）.结论 ABCG2、PKHD1、PDGFB、LPHN3及MC4R基因的多态性与T2DM患者SUA水平相关.     

ETS1基因多态性与原发性干燥综合征的相关性

目的 探讨ETS1基因单核苷酸多态性（single nucleotide polymorphism,SNP）与汉族人群原发性干燥综合征（primary sjōgren＇s syndrome,pSS）遗传易感性是否相关.方法 提取261例pSS患者和597例健康对照者的全基因组DNA.使用Sequenom MassArray方法对ETS1基因上2个SNP位点（rs6590330和rs1128334）进行基因分型.分型结果使用PLINK 1.07软件进行统计分析.结果 rs6590330位点G/G、G/A、A/A基因型频率和G、A等位基因频率分布在pSS组和对照组间差异无统计学意义（均P〉0.05）.加性模型、显性模型、隐性模型下的分析显示,两组间差异仍无统计学意义（均P〉0.05）.将pSS患者按照性别及抗SSA和抗SSB抗体产生情况分组,分析仍未发现任何相关性.rs1128334分型成功率过低无法分析.结论 ETS1基因的SNP位点rs6590330与汉族人群pSS患者遗传易感性不相关.     

Mfn2基因SNP位点rs17037564与肥胖型高血压的相关性研究

目的:探讨中国北方汉族人群中Mfn2基因SNP位点rs17037564与肥胖型高血压的相关性。方法:按照相应入选标准及排除标准收集入选对象,收集高血压患者231例,正常对照对象216例。采集基本临床资料,并对以上对象进行Mfn2基因SNP位点rs17037564基因型进行检测。分析rs17037564不同基因型与超重肥胖患病率以及高血压患病率三者之间相关性。结果:rs17037564 GG+AG基因型对象的高血压患病率明显低于rs17037564 AA基因型的对象,差异具有统计学意义(P=0.02)。rs17037564不同基因型(GG+AG vs.AA)肥胖型高血压的患病率有明显的差异(P0.001)。考虑rs17037564不同基因型对血压的影响后,超重肥胖与高血压患病仍具有显著相关性。(P0.001)。结论:Mfn2基因SNP位点rs17037564与高血压患病可能存在相关性。rs17037564 GG+AG基因型相较于AA基因型是高血压发病的保护性因素,且对肥胖相关的高血压也起到一定的保护性作用。     

细胞色素氧化酶基因CYP1A2多态性与新疆汉族和维吾尔族人群冠心病的相关性

目的 探讨新疆地区维吾尔（维）族人群、汉族人群细胞色素氧化酶基因CYP1A2（cytochrome c oxidase P1A2）多态性与冠心病的关联性。 方法 我们采用两项独立的病例对照研究∶汉族人群389例冠心病患者(病例组）和411名健康体检者（对照组）;维族人群293冠心病患者（病例组）和408名健康体检者（对照组）。通过实时PCR对CYP1A2基因单核苷酸多态性（SNPs）rs2069522和rs2472304进行基因分型。 结果 仅在汉族人群中,SNP1 (rs2069522)基因型的分布在冠心病组和对照组之间差异均有统计学意义(P < 0.05)。而维族人群中未见显著差异。新疆汉族病例组SNP1 (rs2069522)显性模型(CC vs CT + TT)基因型频率显著高于对照组。调整混杂因素后logistic回归分析表明,新疆汉族人群CC基因型患冠心病的风险显著高于CT + TT基因型者(总体:OR = 1.982,95%CI: 1.174～3.236, P < 0.01;男性: OR = 2.671,95%CI: 1.548～4.314, P < 0.01)。 结论 新疆汉族人群CYP1A2基因中rs2069522的位点与冠心病相关。CC基因型可能是新疆汉族人群而非维吾尔族人群发生冠心病的独立危险因素。     

脂蛋白脂酶基因多态性与中青年原发性高血压的相关性研究

目的:探讨中国中青年汉族人群中脂蛋白脂酶(LPL)单核苷酸基因多态性(SNP)与原发性高血压(EH)易感性的关系。方法:根据一定的纳入和排除标准筛选高血压患者及健康体检人群,收集临床资料,采集血液标本,采用TaqMan-MGB法检测LPL基因rs253和rs328位点多态性,分析基因多态性与中青年原发性高血压发病率的相关性。结果:病例组入选499例,对照组入选336例,两组之间性别、年龄、吸烟比例、血肌酐水平差异无统计学意义,饮酒、家族史、血压、血糖等指标有统计学差异。不同基因型在病例组与对照组的分布:rs253位点CC、CT、TT基因型分布有统计学差异(P=0.044),rs328位点等位基因G、C分布频率有统计学差异(P0.001)。将总体按BMI是否25 kg/m~2和是否有血脂异常分层并进行多种基因模型分析,结果显示在中青年肥胖人群(BMI≥25 kg/m~2)中,rs253位点隐性模型CC vs CT+TT中基因型频率分布有统计学差异(P=0.002);在血脂异常的人群中,rs253位点隐性模型CC vs CT+TT基因型频率分布有统计学差异(P=0.020)。Logistic回归分析校正性别、年龄、吸烟、饮酒、家族史、BMI、血脂等多个混杂因素后,结果依然显示,在中青年肥胖人群中,rs253位点隐性模型与高血压发病风险显著相关(P=0.017,OR=0.598,95%CI:0.393～0.912);在有血脂异常的人群中,该模型亦与高血压发病风险相关(P=0.037,OR=0.652,95%CI:0.436～0.975)。结论:在国内中青年汉族肥胖人群以及有血脂异常的人群中,LPL基因rs253位点多态性可能与EH发生相关,该位点CC基因型较CT和TT发病风险明显降低;rs328位点则未见与EH明显相关性。     

Combined effects of FTO rs9939609 and MC4R rs17782313 on obesity and BMI in Chinese Han populations

Genetic variants of FTO and MC4R have been linked with obesity and T2DM in populations of Europeans. In this study, we have investigated the association of FTO rs9939609 and MC4R rs17782313 with obesity and T2DM in the Chinese population and analyzed the relationship between rs9939609 and rs17782313. 2351 individuals were recruited. We tested the rs9939609 and rs17782313 by sequences retrieval method. Clinical and biochemical characteristics were measured. The rs9939609 per-A allele and rs17782313 per-C allele increases of OR for obesity was 1.42 (95% CI 1.39-3.74) and 1.39 (95% CI 1.21-3.53).The genotypic OR for obesity was 1.92 (95% CI 1.81-4.67) for AA genotype, 1.71 (95% CI 1.47-4.54) for AT genotype, 1.87 (95% CI 1.72-4.00) for CC genotype, and 1.44 (95% CI 1.20-3.18) for CT genotype. BMI of participants carrying neither FTO nor MC4R risk allele was 25.9?±?4.9, one risk allele was 26.4?±?5.1, two risk alleles was 28.1?±?5.5, and there or four risk alleles was 33.2?±?6.3. We found no association between FTO and MC4R and the Chinese population with T2DM (P?>?0.05). Our data support that the rs9939609 and rs17782313 are strongly associated with obesity and BMI. Their combined effects were significant in Chinese population. No association between FTO and MC4R and Chinese population with T2DM was found.     

Common polymorphism near the MC4R gene is associated with type 2 diabetes: data from a meta-analysis of 123,373 individuals

Aims/hypothesis  

Genome-wide association studies have shown that variants near the melanocortin 4 receptor gene (MC4R) (rs17782313 and rs12970134) are associated with risk of obesity in Europeans. As obesity is associated with an increased risk of type 2 diabetes, many studies have investigated the association between polymorphisms near the MC4R gene and type 2 diabetes risk across different ethnic populations, with inconsistent results. In this study, we performed a meta-analysis to clarify the association of variants near MC4R with type 2 diabetes risk.     

Naturally occurring mutations in the melanocortin receptor 3 gene are not associated with type 2 diabetes mellitus in French Caucasians

Familial genetic studies of type 2 diabetes (T2DM) of different human populations, including the French Caucasians, suggested evidence for linkage of T2DM and human chromosome 20q13, a region where maps the melanocortin 3 receptor gene (MC3R). Likewise, its homologous MC4R in human obesity, MC3R gene is also a good candidate for genetic susceptibility to glucose intolerance and T2DM. We therefore undertook a molecular study to assess the role of genetic variations of this gene in a large cohort of French families with T2DM. In these patients, we identified two missense mutations in the MC3R gene: Val(81)Ile and Lys(6)Thr. These two variants, which were in complete linkage disequilibrium, were also present in nondiabetic controls. Based on association and familial linkage disequilibrium tests results, we found that these MC3R gene-coding variants were not associated with diabetes or obesity. These variants were found, however, marginally associated with insulin and glucose levels during oral glucose tolerance testing in normoglycemic subjects. Overall, the present study provides no evidence for a major role of the MC3R coding mutations underlying the genetic linkages of T2DM and the MC3R gene region on chromosome 20q13 in T2DM families from France and other geographical origins.     

Genetic variants in ADIPOQ gene and the risk of type 2 diabetes: a case-control study of Chinese Han population

This study was to evaluate the association between ADIPOQ gene variants and type 2 diabetes mellitus (T2DM). TaqMan(?) assay was performed to test the genotypes in T2DM patients (n?=?1,105) and normal control subjects (n?=?1,107). Serum adiponectin concentration was measured by ELISA kit. The variant genotypes rs7649121AT and rs7649121AT/TT, compared with the AA genotype, were associated with a significantly decreased risk of T2DM [Adjusted OR (95% CI)?=?0.79(0.66-0.95), 0.80(0.67-0.96), respectively]. In stratified analysis, rs2241767AG genotype increased the risk of T2DM in obesity group [Adjusted OR (95% CI)?=?1.32(1.03-1.69)]. Patients with genotype AG/GG of rs2241767 had lower levels of serum adiponectin than those with the genotype AA (P?=?0.044). Haplotype analyses were not significant. Crossover analysis of rs7649121 and environmental risk factor (obesity) indicated that the protect effect of rs7649121AT/TT maybe offset by the environmental risk. Those who exposed to environmental risk factor (obesity) had a chance to attack T2DM compared with those who did not expose to the two factors [Adjusted OR (95% CI)?=?1.64(1.30-2.06)]. This study suggested that the ADIPOQ gene polymorphisms were associated with the risk of T2DM in a Chinese Han population.     

Association of MC4R (rs17782313) gene polymorphism with obesity measures in Western India

Background and aimsThe association of melanocortin receptor 4 (MC4R) gene with adiposity measures is widely studied in European populations. Only six studies have investigated the role of MC4R gene with adiposity measures among Indian populations. We have evaluated the role of MC4R (rs17782313) gene polymorphism in influencing adiposity measures in India among children and adults.Materials and methodsThe present population based cross sectional study was conducted among 303 individuals (208 children and 95 adults) of age group 10–30 years, belonging to Rajasthan. Somatometric measurements (standing height, weight, and waist and hip girths) and blood samples were taken after obtaining written informed consent. Genotyping of MC4R rs17782313 single nucleotide polymorphism was done using restriction fragment length polymorphism method for polymerase chain reaction ampli?ed fragments. We examined association between rs17782313 and different adiposity measures (height, weight, BMI, WHR, and waist and hip girths) using linear regression models.ResultsThe MC4R variant (rs17782313) predicted increased body weight (0.15 kg, S.E ± 0.076, P = 0.043) among children. In combined population, the rs17782313 variant was moderately associated with body weight (0.13 kg, S.E ± 0.070, P = 0.057). This variant was not found to be associated with any other adiposity measure.ConclusionFurther studies are needed to evaluate the association of MC4R variants through sequencing and functional genomics with different adiposity measures in Indian populations for understanding the genetic underpinnings of adiposity in India.     

Association study between chromosome 10q26.11 and obesity among Swedish men

OBJECTIVE: Proximal chromosome 10q26 was recently linked to waist/hip ratio in European and African-American families. The objective was to investigate whether genomic variation in chromosome 10q26.11 reflects variation in obesity-related clinical parameters in a Swedish population. DESIGN: Genetic association study of single-nucleotide polymorphisms (SNPs) in chromosome 10q26.11 and obesity-related clinical parameters was performed. Obesity was defined as body mass index (BMI) > or = 30 kg/m2. SUBJECTS: Swedish Caucasians comprising 276 obese and 480 nonobese men, 313 obese and 494 nonobese women, 177 obese and 163 nonobese patients with type 2 diabetes mellitus (T2DM), and 106 obese and 201 nonobese subjects with impaired glucose tolerance (IGT) patients. MEASUREMENTS: Genotypes of 11 SNPs at chromosome 10q26.11, and various obesity-related clinical parameters. RESULTS: Homozygosity of a common haplotype constructed by three SNPs, rs2185937, rs1797 and hCV1402327, covering an interval of 2.7 kb, was suggested to confer an increased risk for obesity of 1.5 among men (P = 0.043). The C allele frequency and homozygous genotype frequency of the rs1797 tended to be higher among obese compared to among nonobese men (P = 0.017 and 0.020, respectively). The distribution of BMI and diastolic blood pressure was higher among those with the C/C genotype (P = 0.022 and 0.0061, respectively). The obese and the nonobese groups were homogeneous over BMI subgroups with regard to rs1797 risk genotype distribution. There was no tendency for association between rs1797 and obesity among neither women nor T2DM nor IGT patients. CONCLUSION: We show support for association between proximal chromosome 10q26.11 and obesity among Swedish men but not women through the analysis of a haplotype encompassing 2.7 kb.     

Pro-opiomelanocortin gene is associated with serum leptin levels in lean but not in obese individuals

OBJECTIVE: Mutations in the pro-opiomelanocortin and melanocortin 4 receptor genes (POMC and MC4R) cause monogenic obesity, and the POMC locus (2p21) has been linked to leptin levels and body mass index (BMI). We searched for monogenic obesity due to mutations in POMC and MC4R among morbidly obese Swedes and studied the association of POMC variants with BMI and serum leptin levels. DESIGN: MC4R and POMC were screened for mutations in 102 obese Swedish subjects (40+/-11 y, 41.3+/-5.0 kg/m(2)) using the single-strand conformation polymorphism technique. The detected polymorphisms were genotyped in 118 lean control subjects (56+/-11 y, 22.6+/-1.3 kg/m(2)) and studied for association with BMI and serum leptin levels. RESULTS: No cases of monogenic obesity due to mutations in POMC or MC4R were identified and none of the four common POMC polymorphisms (RsaI, ins56, Glu188Gly and C8246T) were associated with obesity. Lean carriers of the C8246T CC-genotype had higher serum leptin levels compared to CT or TT carriers (9.7+/-6.6 vs 6.7+/-4.4 microg/l, P=0.003 for leptin levels adjusted for age, sex and BMI in regression analysis), especially lean females (P=0.004) and lean female carriers with the C8246T(CC)/RsaI(--or +-) genotype combinations (P<0.0005). Neither the C8246T CC-genotype nor the C8246T(CC)/RsaI(--or +-) were associated with serum leptin levels in obese subjects. CONCLUSIONS: Monogenic forms of obesity due to mutations in POMC and MC4R are rare in Swedish obese patients. Polymorphisms in POMC are associated with variation in serum leptin levels within the normal range in healthy lean but not in obese individuals.     

UCP3及SUR1基因多态性与我国北方地区汉族人群肥胖及相关表型的关系

目的采用病例-对照研究,探讨解偶联蛋白3（UCP3）Tyr210Tyr（C→T）和磺脲类受体1[ABCC8（SUR1）]Ser1370Ala（T→G）单核苷酸多态性（SNP）与肥胖及血清脂质、FPG等肥胖相关数量表型的关系。方法选取我国北方地区汉族人群中超重及肥胖患者（BMI≥25．O）300例;另入选300例年龄、性别匹配的正常体重者（18．5≤BMI〈25．0）为对照组。测定血浆脂质和FPG等肥胖相关数量表型;并采用实时荧光定量PCR技术,检测UCP3Tyr210Tyr（C→T）和SUR1Ser1370Ala（T→G）多态性基因型。结果（1）UCP3Tyr210Tyr（C→T）多态性基因型和等位基因频率在病例组和对照组分布无显著差异且与肥胖及其相关表型无关。（2）SUR1Ser1370Ala（T→G）的C／C、C／T和T／T基因型及等位基因频率在女性的病例组与对照组存在差异（P〈0．05）,而在男性组却无统计学差异;在病例组和对照组中的分布存在差异（P〈0．05）,病例组TT基因型及等位基因频率高于对照组;而仅按性别分层后也未发现基因型在两组间存在差异。由单变量及多变量逐步条件logistic回归分析皆显示SUR1基因Ser1370Ala（T→G）多态性与肥胖相关（P〈0．05）。发现TG和GG基因型频率越高则发生肥胖的可能性越小,TT基因型则相反是肥胖发生的危险因素（ORTG=0．549;ORGG=0．486）。多元线性回归分析发现：各基因型之间的生化指标除LDL—C（P〈0．05）外,其余各指标无统计学差异。按病例对照分层,肥胖组的各基因型之间TG、LDL-C和Glu均值水平存在差异（P〈0．05）,而TC、HDL—C水平的差异无统计学意义。体重正常组各基因型之间TG、LDL-C和Glu、TC、HDL—C平均值水平的差异无统计学意义。按性别进行分层后,发现除男性各基因型的DBP、TG、LDL-C水平存在差异（P〈0．05）,女性各基因型的TG、TC、LDL—C水平和BMI均值存在差异（P〈0．05）?