UCP2-866G/A和ADIPOQ+45T/G基因多态性的交互作用与2型糖尿病合并冠心病发病风险的关系

目的:探讨UCP2-866G/A和ADIPOQ+45T/G基因多态性的交互作用与2型糖尿病合并冠心病发病风险的关系。方法:随机选取2014年10月至2015年5月在佳木斯大学附属第一医院就诊的130例单纯2型糖尿病患者和128例2型糖尿病合并冠心病患者进行病例对照研究。分别采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法和聚合酶链反应-高分辨率溶解曲线(PCR-HRM)方法检测UCP2-866G/A和ADIPOQ+45T/G的基因多态性,并用非条件Logistic回归分析两基因间的交互作用。结果:在两组间分别进行UCP2-866G/A和ADIPOQ+45T/G基因多态性的单独关联分析,两变异位点的基因型和等位基因的频率在两组间的分布及遗传模型关联分析均无统计学差异(P0.05)。两变异位点联合分析发现,UCP2-866 G/A的GG、GA分别和ADIPOQ+45T/G的TG在2型糖尿病合并冠心病中存在正向交互作用(P=0.000,OR_I=OR_(AB)/(OR_A×OR_B)=30.533/(0.549×0.116)1;P=0.007,OR_I=OR_(AB)/(OR_A×OR_B)=13.914/(0.525×0.116)1。结论:该研究显示:UCP2-866G/A和ADIPOQ+45T/G单一基因的多态性与2型糖尿病合并冠心病患病风险无关,而两者之间的交互作用可能增加2型糖尿病合并冠心病的发病风险。     

解偶联蛋白-866G/A基因多态性与肥胖关联性的Meta分析

目的:近年来,关于UCP2-866G/A基因多态性与肥胖关系的研究较多,但各研究的结果不尽一致.本文拟采用Meta分析的方法,对已公开发表的有关UCP2-866G/A基因多态性与肥胖的研究进行系统综合定量分析,以期科学的评价UCP2-866G/A基因多态性与肥胖的关系.方法:本研究运用计算机检索万方全文数据库、中国知网、维普数据库、中国生物医学文献数据库、PubMed等数据库收集关于UCP2-866G/A基因多态性与肥胖相关的公开发表的文献,选择OR值及其95％CI作为Meta分析指标.利用Stata10.0软件对各研究结果进行异质性检验和效应值合并计算.结果:根据统一的纳入和剔除标准,纳入14篇文献,共有肥胖者5195例,对照组9735人.在总人群中,UCP2-866G/A位点A/G的OR=0.931 (95％CI:0.884-0.980),AA+GA/GG的OR=0.924 (95％CI:0.859-0.994),AA/GG的OR=0.886 (95％CI:0.797-0.985),GA/GG的OR=0.925 (95％CI:0.856-0.999),有统计学意义.在欧洲人群中,UCP2-866G/A位点A/G的OR=0.912 (95％CI:0.857-0.970),AA+GA/GG的OR=0.882 (95％CI:0.808-0.962),AA/GG的OR=0.846 (95％CI:0.743-0.963),GA/GG的OR=0.893(95％CI:0.814-0.980),有统计学意义.但在亚洲人群中均无统计学意义.结论:我们认为-866G/A基因多态性与欧洲人群的肥胖有关,与亚洲人群的肥胖无关.     

UCP2启动子-866G/A与APOEε 4多态性在糖尿病肾病发生中的协同效应

目的:探讨解耦联蛋白2基因(UCP2)启动子变异-866G/A及载脂蛋白E与北京人群糖尿病肾病(DN)的发生关联和协同效应.方法:基于聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)技术,对228例DN患者,243例非DN的2型糖尿病患者及78例正常对照进行基因分型,同时进行体格检查和生化指标测定,数据处理使用SPSS(version16.0)完成,用Hardy-Weinberg平衡检验评价人群代表性,按照加性模型分析基因型的整体分布规律,隐性模型和显性模型分析风险等位基因与疾病的关联,通过Logistic回归分析基因变异间的交互作用,分层分析评估其相互作用对DN的贡献.结果:加性模型分析提示UCP2基因-866G/A在DN组和DM组间的分布差异达到统计学显著性(P＜0.001),进一步通过显性模型发现-866A同DN存在正关联,调整年龄和性别混杂后,正关联仍然存在(OR=1.814,95％CI:1.148-2.867).UCP2×APOE交互项和DN存在独立于年龄、性别、体质指数、血糖、甘油三酯等血脂指标的正关联,二者存在效应的协同作用.分层分析表明UCP2基因-866A是独立APOEε4的DN的危险因素,且APOEε4对UCP2基因-866A存在异位显性(epistasis)关系.结论:UCP2基因启动子-866A等位基因和APOEε4等位基因是北京汉族人群DN的风险等位基因,APOEε4存在异位显性,二者效应存在叠加.     

中国汉人纤维蛋白原β链基因-148C/T,-455G/A多态性与冠心病关系的Meta分析

有关中国汉人纤维蛋白原β链基因多态性与冠心病关系的研究屡见报道,但不同的研究之间结果存在一定的差异.本研究根据相应的入选条件,通过文献检索收集中国汉人纤维蛋白原β链基因-148C/T,455G/A多态性与冠心病关系的病例-对照研究,剔除不符合要求的文献,对入选文献进行一致性检验并根据检验结果进行数据合并荟萃(Meta)分析,计算总OR值.共13篇文献符合要求纳入研究,其中7篇关于-148C/T多态性研究包括1488例冠心病患者和1234例对照人群,9篇关于-455G/A多态性的研究包括1023名患者和1081名对照者,入选研究无明显发表偏倚,入选研究的同质性检验显示各研究结果间存在明显的异质性,数据合并结果显示-148C/T多态性位点C/T T/T比C/C的OR值为1.31,95%CI为0.94~1.84(P=0.11),-455G/A多态性位点G/A A/A比G/G的OR值为1.75,95%CI为1.24~2.46(P=0.001).本研究的初步结果显示纤维蛋白原β链基因-455G/A多态性与中国汉人冠心病易感性相关,-455A等位基因可能是冠心病的遗传易感基因,-148C/T基因多态性与中国汉人冠心病易感性无明显关系.     

脂联素基因SNP45 T/G多态性与2型糖尿病相关性研究

目的:探讨脂联素基因(APM1)SNP45 T/G多态性与湖北汉族人群2型糖尿病的相关性.方法:采用聚合酶链反应-限制性片断长度多态性(PCR-RFLP)方法分析了479例样本的APM1基因SNP45T/G多态性,并测定身高、体重、腰围、臀围、血压和空腹血糖等生理指标.结果:两种实验设计中对照组与病例组基因型和等位基因频率差异均无统计学意义.结论:脂联素基因SNP45T/G多态性在湖北汉族人群2型糖尿病的发生发展中可能不起主要作用.     

中国汉人纤维蛋白原β链基因-148C／T,-455G／A多态性与冠心病关系的Meta分析

有关中国汉人纤维蛋白原β链基因多态性与冠心病关系的研究屡见报道,但不同的研究之间结果存在一定的差异．本研究根据相应的入选条件,通过文献检索收集中国汉人纤维蛋白原β链基因-148C／T,455G／A多态性与冠心病关系的病例-对照研究,剔除不符合要求的文献,对入选文献进行一致性检验并根据检验结果进行数据合并荟萃（Meta）分析,计算总OR值．共13篇文献符合要求纳入研究,其中7篇关于-148C／T多态性研究包括1488例冠心病患者和1234例对照人群,9篇关于-455G／A多态性的研究包括1023名患者和1081名对照者,入选研究无明显发表偏倚,入选研究的同质性检验显示各研究结果间存在明显的异质性,数据合并结果显示-148C／T多态性位点C／T＋T／T比C／C的OR值为1．31,95％CI为0．94-1．84（P=0．11）,-455G／A多态性位点G／A＋A,A比G／G的OR值为1．75,95％CI为1．24-2．46（P=0．001）．本研究的初步结果显示纤维蛋白原B链基因-455G／A多态性与中国汉人冠心病易感性相关,-455A等位基因可能是冠心病的遗传易感基因,-148C／T基因多态性与中国汉人冠心病易感性无明显关系．     

XPA 及XPG 基因多态性与晚期非小细胞肺癌铂类药物化疗疗效及 预后的关系

目的:研究DNA修复基因XPAA23G及XPGC46T位点基因多态性与晚期非小细胞肺癌铂类化疗疗效及预后的关系。方法:经病理学确诊的晚期非小细胞肺癌患者89例,化疗前提取其外周血DNA,用DNA测序技术检测XPA、XPG基因型,所有患者均接受2-4个周期铂类药物为基础的化疗。结果:1)89例患者中,携带XPA23A/A及A/G+G/G基因型的化疗有效率分别为47.5%和24.5%,差异有统计学意义(x2=5.137,P=0.023);携带XPG46C/C及C/T+T/T基因型的患者治疗有效率分别为47.6%、23.4%,二者间也有统计学差异(x2=5.729,P=0.017),联合分析显示A/A及C/C型化疗有效率最高,达63.0%,而A/A及C/T+T/T型最低,仅15.4%,四组间有显著统计学差异(x2=14.080,P=0.003)。2)89例患者中位TTP为7个月,XPA23A/A基因型中位TTP为11个月,A/G+G/G基因型为6个月,两者比较差异有显著性(x2=44.640,P<0.01);XPG46C/C基因型中位TTP为10个月,C/T+T/T基因型为6个月,两者也有统计学差异(x2=32.236,P<0.01)。联合分析显示,XPAA/A+XPGC/C型中位TTP最长,达到11个月,而A/G+G/G及C/T+T/T基因型最短,仅有4个月,四组间差异有显著统计学意义(x2=59.295,P<0.01)。结论:XPAA23G及XPGC46T单核苷酸多态性可单独及联合用于预测晚期NSCLC病人对铂类药物的化疗疗效及TTP,初步提示可以根据患者基因型来指导个体化治疗。     

脂联素基因SNP45T／G多态性与2型糖尿病相关性研究

目的：探讨脂联素基因（APM1）SNP45T／G多态性与湖北汉族人群2型糖尿病的相关性。方法：采用聚合酶链反应．限制性片断长度多态性（PCR—RFLP）方法分析了479例样本的APM1基因SNP45T／G多态性,并测定身高、体重、腰围、臀围、血压和空腹血糖等生理指标。结果：两种实验设计中对照组与病例组基因型和等位基因频率差异均无统计学意义。结论：脂联素基因SNP45T／G多态性在湖北汉族人群2型糖尿病的发生发展中可能不起主要作用。     

脂联素基因单核苷酸多态性T45G与湖北汉族人2型糖尿病的遗传关联研究

采用病例.家系对照和随机病例.对照两种设计,分析了603例样本脂联素基因(Adiponectin,APMl)单核苷酸多态性(SNP)rs13061862(T45G)与湖北汉族人群2型糖尿病的相关性.在所有样本中,2型糖尿病病人的G等位基因及GG基因型频率显著高于正常人(G:42.0%比21.7%,P<0.001;GG:13.6%比4.5%,P=0.032);在180个病例.家系对照中,2型糖尿病患者的GG基因型频率显著高于对照组(GG:17.8%比5.6%,P=0.011);在423个随机病例.对照中,2型糖尿病患者GG基因型频率也显著高于对照组(GG:12.2%比3.9%,P=0.025);单因素Logistic回归分析显示,GG基因型是2型糖尿病的危险因子(OR=3.58,95%C/=1.70-7.54).这些结果表明,脂联素基因SNPT45G多态性与湖北汉族人群2型糖尿病的发生发展相关,GG基因型是中国湖北汉族人2型糖尿病的遗传危险因素.     

2 型糖尿病家系患者PON2 基因9 Ser311C→G 多态性的研究*

目的:研究黑龙江地区汉族人2型糖尿病家系的PON2基因9 Ser311C→G多态性,探讨其与2型糖尿病发病的关系。方法:应用聚合酶链式反应-限制性内切酶长度多态性(PCR-RFLP)技术,对来自于黑龙江地区120个2型糖尿病家系中的210例2型糖尿病患者及319例正常对照的PON2基因9 Ser311→Cys(C→G)位点进行基因分型。结果:PON2基因9 Ser311C→G三种基因型在病例组和对照组间整体分布没有统计学意义(P=0.610,df=2);各基因型及等位基因在病例组和对照组间分布没有统计学意义(P>0.05)。结论:PON2基因9 Ser311C→G多态性与黑龙江地区汉族人2型糖尿病无关,PON2基因可能不是中国人2型糖尿病发病的相关易感基因。     

Association of +45(T/G) and +276(G/T) polymorphisms in the adiponectin gene with coronary artery disease in a population of Iranian patients with type 2 diabetes

The relation of Two single nucleotide polymorphisms (SNPs) at the adiponectin locus (+45T/G and +276G/T) with coronary artery disease (CAD) is controversial. The aim of the present study was to evaluate the genetic influence of the adiponectin gene polymorphisms in the development of CAD among patients with Type 2 diabetes (T2D). The adiponectin genotypes were detected by polymerase chain reaction and restriction analysis (PCR-RFLP) in our patients. Two adiponectin gene (ADIPOQ) SNPs (i.e. SNPs +45T>G and +276G>T) were genotyped in 114 Type 2 diabetic subjects with CAD, and 127 Type 2 diabetic patients without CAD. Demographic and anthropometric data along with plasma biochemistry including lipids, glycemic indices, and adiponectin were collected. There was a significant difference in the distribution of genotypes of +45T/G and +276G/T between CAD and non-CAD individuals (P < 0.05). Based on our results SNP+276G>T is associated with decreased risk of CAD after adjustment for potential confounding factors [adjusted OR = 0.39 (95%CI: 0.22–0.68); P = 0.001]. Similar findings were not observed for the +45T>G SNP. Two haplotypes 45T-276T and 45G-276T were associated with a decreased risk of CAD [adjusted OR = 0.47 (95% CI: 0.32–0.94); P = 0.03 and adjusted OR = 0.33 (95% CI: 0.13–0.83); P = 0.02 respectively]. No significant difference was observed between HOMA-IR, BMI, waist circumference, history of hypertension, HbA1C, and lipid concentrations regarding the two SNPs. In conclusion, these findings suggest that T allele of +276G>T SNP is significantly associated with decreased risk of CAD in T2D Patients. Also Haplotype analysis showed that two haplotypes 45T-276T and 45G-276T were associated with a decreased risk of CAD.     

Uncoupling protein 2 − 866G/A and uncoupling protein 3 − 55C/T polymorphisms in young South African Indian coronary artery disease patients

Background

Uncoupling proteins (UCPs) 2 and 3 play an important role in the regulation of oxidative stress which contributes to chronic inflammation. Promoter polymorphisms of these genes have been linked to chronic diseases including heart disease and type II diabetes mellitus in several populations. This is the first investigation of the UCP2 − 866G/A rs659366 and UCP3 − 55C/T rs1800849 polymorphisms in young South African (SA) Indians with coronary artery disease (CAD).

Methods

A total of 300 subjects were recruited into this study of which 100 were SA Indian males with CAD, 100 age- (range 24–45 years), gender- and race-matched controls and 100 age-matched black SA males. The frequency of the UCP2 − 866G/A and UPC3 − 55C/T genotypes was assessed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP).

Results

The heterozygous UCP2 − 866G/A and homozygous UCP3 − 55C/C genotypes occurred at highest frequency in CAD patients (60% and 64%, respectively) compared to SA Indian controls (52% and 63%) and SA Black controls (50% and 58%). The UCP2 − 886G/A (OR = 1.110; 95% CI = 0.7438–1.655; p = 0.6835) and UCP3 − 55C/T (OR = 0.788; 95% CI = 0.482–1.289; p = 0.382) polymorphisms did not influence the risk of CAD.The rare homozygous UCP3 − 55T/T genotype was associated with highest fasting glucose (11.87 ± 3.7 mmol/L vs. C/C:6.11 ± 0.27 mmol/L and C/T:6.48 ± 0.57 mmol/L, p = 0.0025), HbA1c (10.05 ± 2.57% vs. C/C:6.44 ± 0.21% and C/T:6.76 ± 0.35%, p = 0.0006) and triglycerides (6.47 ± 1.7 mmol/L vs. C/C:2.33 ± 0.17 mmol/L and C/T:2.06 ± 0.25 mmol/L, p < 0.0001) in CAD patients.

Conclusion

The frequency of the UCP2 − 866G/A and UCP3 − 55C/T polymorphisms was similar in our SA Indian and SA Black groups. The presence of the UCP2 − 866G/A and UCP3 − 55C/T polymorphisms does not influence the risk of CAD in young South African Indian CAD patients.     

Association study of the single nucleotide polymorphisms in adiponectin-associated genes with type 2 diabetes in Han Chinese

Single-nucleotide polymorphisms （SNPs） of ADIPOQ, ADIPOR1, and ADIPOR2 have been associated with type 2 diabetes mellitus （T2DM）, but there are many conflicting results especially in Chinese populations. To investigate the contribution of the adiponectin genes and their receptors to T2DM, a case-control study was performed and 11 SNPs ofADIPOQ, ADIPOR1, and ADIPOR2 were genotyped in 985 T2DM and 1,050 control subjects, rs 16861194 （-11426 A〉G） in the putative promoter of ADIPOQ was associated with T2DM （P = 0.007; OR = 1.29, 95% CI 1.08-1.55）. None of the other 10 SNPs were associated with T2DM in this study, although rs2241766 and rs1501299 were reported to be associated with T2DM in previous Chinese studies. There was also no significant difference found from the ADIPOQ haplotype analysis, which contains rs 16861194. In addition, we also assessed potential gene-gene interactions in three genes and no interactions were found. In conclusion, our results supported the ADIPOQ gene as a possible risk factor for type 2 diabetes in Han Chinese population.     

Haplotypes in the promoter region of the ADIPOQ gene are associated with increased diabetes risk in a German Caucasian population.

Adiponectin, which is encoded by the ADIPOQ gene, has been shown to modulate insulin sensitivity and glucose homeostasis. Plasma adiponectin levels are decreased in type 2 diabetes and obesity. Genetic variations within the ADIPOQ gene are associated with decreased adiponectin hormone levels. To analyze specific single-nucleotide polymorphisms (SNPs) and their association with T2D, 365 German subjects with T2D and 323 control subjects were screened. Three common SNPs - +45T>G in exon 2, and 2 promoter variants SNPs -11391G>A and -11377C>G - were analyzed. We found that the variant allele of SNP -11391G>A was significantly more frequent in the diabetic patient group than in the control group (p=0.003). Carrying the haplotype of SNP -11391A and SNP -11377C was associated with a 1.50-fold (p=0.03) increase in diabetes risk. The combination of the A-C haplotype and the G-C haplotype was associated with significantly elevated diabetes risk (OR=2.82 (95% CI: 1.35-5.91), p=0.006) after correction for BMI and age. Our observations suggest that diploid combinations of haplotype in the adiponectin gene promoter region contribute to the genetic risk of T2D in individuals from a German Caucasian population.     

Lack of evidence for intermolecular epistatic interactions between adiponectin and resistin gene polymorphisms in Malaysian male subjects

Epistasis (gene-gene interaction) is a ubiquitous component of the genetic architecture of complex traits such as susceptibility to common human diseases. Given the strong negative correlation between circulating adiponectin and resistin levels, the potential intermolecular epistatic interactions between ADIPOQ (SNP+45T > G, SNP+276G > T, SNP+639T > C and SNP+1212A > G) and RETN (SNP-420C > G and SNP+299G > A) gene polymorphisms in the genetic risk underlying type 2 diabetes (T2DM) and metabolic syndrome (MS) were assessed. The potential mutual influence of the ADIPOQ and RETN genes on their adipokine levels was also examined. The rare homozygous genotype (risk alleles) of SNP-420C > G at the RETN locus tended to be co-inherited together with the common homozygous genotypes (protective alleles) of SNP+639T > C and SNP+1212A > G at the ADIPOQ locus. Despite the close structural relationship between the ADIPOQ and RETN genes, there was no evidence of an intermolecular epistatic interaction between these genes. There was also no reciprocal effect of the ADIPOQ and RETN genes on their adipokine levels, i.e., ADIPOQ did not affect resistin levels nor did RETN affect adiponectin levels. The possible influence of the ADIPOQ gene on RETN expression warrants further investigation.     

Distribution and genotype frequency of adiponectin (+45 T/G) and adiponectin receptor2 (+795 G/A) single nucleotide polymorphisms in Iranian population

The Adiponectin (ADIPOQ) gene encodes adipose tissue-secreted hormone, Adiponectin, which is secreted to the bloodstream by adipocytes. Adiponectin is a hormone with anti-inflammatory and anti-atherogenic properties and plays a significant role in insulin sensitivity and obesity. The genetic variations in ADIPOQ gene change the circulating adiponectin level and may cause insulin resistance. The aim of the present study is to evaluate the frequency of a common single nucleotide polymorphism (SNP) of ADIPOQ gene (+45T/G) and adiponectin receptor-2 (ADIPOR2) gene (+795G/A) in Iranian population and to correlate these data with other populations. A hundred healthy volunteers were enrolled to identify the genotype of ADIPOQ gene (+45T/G) and ADIPOR2 gene (+795G/A). This was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotype frequencies for ADIPOQ (+45T/G) were 0.789 for TT, 0.164 for TG, and 0.0468 for GG. Allelic frequencies were 0.87 and 0.13 for T and G, respectively. Genotype frequencies for ADIPOR2 (+795G/A) were 0.09 for AA, 0.3 for AG, and 0.61 for GG; allelic frequencies were 0.24 for A and 0.76 for G. Comparisons between ADIPOQ and ADIPOR2 polymorphisms in Iranian population with those in other populations showed significant differences.     

Interaction between the <Emphasis Type="Italic">UCP2</Emphasis>–866G/A,mtDNA 10398G/A and <Emphasis Type="Italic">PGC1α</Emphasis> p.Thr394Thr and p.Gly482Ser polymorphisms in type 2 diabetes susceptibility in North Indian population

In the recent past, we have observed a possible role of 10398A and 16189C mtDNA and PGC1α p.Thr394Thr (rs2970847) and p.Gly482Ser (rs8192673) variant genotypes providing susceptibility/protection against type 2 diabetes mellitus (T2DM) in two North Indian population groups. These initial observations encouraged us to look at the candidate genes in combination with –866G/A (rs659366) polymorphism in uncoupling protein 2 (UCP2) in a single study of a relatively large sample size, constituted of both the cohorts, to unravel an interesting outcome of an additive interaction in-between the studied genes. In a total of 1,686 individuals (762 cases and 924 controls) belonging to Indo-European linguistic group from North India, a comparison of risk genotype combinations of: UCP2–866GG, mtDNA 10398A and PGC1α p.Thr394Thr or p.Gly482Ser against the protective genotypes: UCP2–866XA, mtDNA 10398G and PGC1α p.Thr394Thr (nominal P value = 1.75 × 10⁻¹⁴, Odds ratio, OR = 5.29, 3.40–8.22 at 95% CI) or PGC1α p.Gly482Ser (nominal p value = 4.42 × 10⁻²⁴, OR = 8.59, 5.53–13.35 at 95% CI), showed a highly significant difference and increased ORs. In a complex disease, it is always encouraging to find an additive interaction of multiple small effects of the studied candidate gene variations. An erratum to this article is available at .     

An association between − 866G/A polymorphism in the promoter of UCP2 and obesity: A meta-analysis

− 866G/A polymorphism in the promoter of UCP2 gene has been reported to be associated with obesity, but the results remain inconclusive. To assess the relation of UCP2 − 866G/A polymorphism and obesity susceptibility, a meta-analysis was performed. PubMed, ISI, Wanfang database, VIP and CBM were searched to identify relevant studies up to July 31, 2012. Odds ratios (OR) and 95% confidence interval (95% CI) were pooled using fixed or random effect models. Subgroup analysis was performed by ethnicity (categorized as Asian and European). Heterogeneity and publication bias evaluation were performed to validate the credibility. Meta-regression and the ‘leave one out’ sensitive analysis were used to explore the potential sources of between-study heterogeneity. 14 studies were included in this meta-analysis. After exclusion of articles that deviated from the HWE in controls, and were the key contributors to between-study heterogeneity, the meta-analysis showed a significant association of the A allele with reduced risk of obesity in overall analysis and in European in the dominant, codominant and additional models. In Asian, no significant association was found between the − 866G/A in UCP2 gene and obesity susceptibility. The meta-analysis suggested that UCP2 − 866G/A polymorphism was associated with obesity. The A allele may be an important protective factor for obesity in European, but not in Asian. Further studies are needed to elucidate the relationship.     

Associations between UCP1 -3826A/G,UCP2 -866G/A,Ala55Val and Ins/Del,and UCP3 -55C/T Polymorphisms and Susceptibility to Type 2 Diabetes Mellitus: Case-Control Study and Meta-Analysis

Background

Some studies have reported associations between five uncoupling protein (UCP) 1–3 polymorphisms and type 2 diabetes mellitus (T2DM). However, other studies have failed to confirm the associations. This paper describes a case-control study and a meta-analysis conducted to attempt to determine whether the following polymorphisms are associated with T2DM: -3826A/G (UCP1); -866G/A, Ala55Val and Ins/Del (UCP2) and -55C/T (UCP3).

Methods

The case-control study enrolled 981 T2DM patients and 534 nondiabetic subjects, all of European ancestry. A literature search was run to identify all studies that investigated associations between UCP1–3 polymorphisms and T2DM. Pooled odds ratios (OR) were calculated for allele contrast, additive, recessive, dominant and co-dominant inheritance models. Sensitivity analyses were performed after stratification by ethnicity.

Results

In the case-control study the frequencies of the UCP polymorphisms did not differ significantly between T2DM and nondiabetic groups (P>0.05). Twenty-three studies were eligible for the meta-analysis. Meta-analysis results showed that the Ala55Val polymorphism was associated with T2DM under a dominant model (OR = 1.27, 95% CI 1.03–1.57); while the -55C/T polymorphism was associated with this disease in almost all genetic models: allele contrast (OR = 1.17, 95% CI 1.02–1.34), additive (OR = 1.32, 95% CI 1.01–1.72) and dominant (OR = 1.18, 95% CI 1.02–1.37). However, after stratification by ethnicity, the UCP2 55Val and UCP3 -55C/T alleles remained associated with T2DM only in Asians (OR = 1.25, 95% CI 1.02–1.51 and OR = 1.22, 95% CI 1.04–1.44, respectively; allele contrast model). No significant association of the -3826A/G, -866G/A and Ins/Del polymorphisms with T2DM was observed.

Conclusions

In our case-control study of people with European ancestry we were not able to demonstrate any association between the UCP polymorphisms and T2DM; however, our meta-analysis detected a significant association between the UCP2 Ala55Val and UCP3 -55C/T polymorphisms and increased susceptibility for T2DM in Asians.