Variants of calpain-10 gene and its association with type 2 diabetes mellitus in a Chinese population

Variants of calpain-10 gene (CAPN 10) have recently been reported to be associated with type 2 diabetes (T2DM). Haplotype combination 112/121 defined by three single nucleotide polymorphisms (SNPs) (UCSNP-43, -19 and -63) of CAPN 10 conferred the highest risk for T2DM in Mexican-Americans. In this study, we aim to examine whether these genetic variants contribute to the susceptibility for T2DM in a Chinese population. The frequencies of these three SNPs were determined in 168 patients with T2DM and 104 controls. Distribution of alleles, genotypes and haplotypes at three loci were not significantly different between the two groups. No difference was observed in the 112/121 haplotype combination distribution. However, haplotype combination 112/221 was more prevalent in the control group than in T2DM group (16.35% versus 7.14%, p = 0.025). Control subjects with haplotype combination 112/121 had higher serum cholesterol level than others without haplotype combination 112/121 (5.7 +/- 1.4 versus 5.2 +/- 0.7, p = 0.011). Our results suggest that haplotype combination 112/221 associated with reduced risk for T2DM and haplotype combination 112/121 might be a risk factor for increased serum cholesterol in Chinese population.     

Vitamin D receptor gene polymorphisms and association with type 2 diabetes mellitus in a Polish population.

Vitamin D plays an important role in insulin secretion. There is also evidence that this steroid may influence the insulin sensitivity. Thus genes involved in its metabolic pathway have been regarded as good candidates for type 2 diabetes mellitus (T2DM). One of them is vitamin D receptor gene (VDR). Its multiple polymorphisms have been examined for the association with T2DM in several populations. Those studies did not provide clear answers about the role of VDR in this disease. The aim of the study was to search for the association of FokI, ApaI, BsmI, and TaqI polymorphisms of VDR gene with T2DM in a Polish population using a case-control study design. Overall, 548 individuals were examined: 308 T2DM patients and 240 control individuals. The study groups were genotyped for VDR FokI, ApaI, BsmI, and TaqI variants using the restriction fragment length polymorphism (RFLP) method. Since variants of ApaI, BsmI, and TaqI polymorphisms were in very strong linkage disequilibrium, three loci haplotypes could be assigned to phase-unknown individuals with a high degree of confidence. Differences in allele, genotype, haplotype, and haplotype combination distribution between the groups were examined by chi2 test. The VDR allele frequencies for T2DM patients and controls were as follows: FokI-F/f - 53.4 %/46.6 % vs. 55.2 %/44.8 %, BsmI-B/b - 34.4 %/65.6 % vs. 37.5 %/62.5 %, ApaI-A/a - 47.9 %/52.1 % vs 50.9 %/49.1 %, TaqI-T/t - 67.6 %/32.4 % vs. 62.7 %/37.3 %, respectively. There was no difference between the groups in allele frequency. Similarly, distribution of genotypes, three locus BsmI/ApaI/TaqI haplotypes and their combinations were similar in the groups. In conclusion, our study did not provide evidence for the association of four examined VDR polymorphisms with T2DM in a Polish population. We postulate that to fully determine whether the sequence differences in VDR gene are susceptibility variants for T2DM, additional studies in different populations are required in a large study group.     

中国人群2型糖尿病与脂联素基因单核苷酸多态性关系的Meta分析

目的 综合评价中国人群脂联素基因(apM1)单核苷酸多态性(SNP)与2型糖尿病的关系.方法 应用Meta分析软件包RevMan4.3.1对各研究结果进行数据合并,计算SNP基因型频数分布合并后OR值及其95%CI;利用Egger分析和失安全系数(Nfs<,0.05>)评估发表偏倚;对各研究结果进行不同分析模式和样本含量的敏感性分析,评价Meta分析结果的稳定性.结果 检索筛选到相关文献9篇.apM1基因的SNP45在各研究间存在显著的异质性(P<0.10).亚组分析表明apM1基因SNP45在以南方人群为对象的研究间异质性较大(P<0.01),是异质性的主要来源.apM1等位基因或基因型SNP45G和SNP45GG、SNP276G和SNP276GG在中国2型糖尿病人群的分布频率显著高于正常糖耐量组,其合并OR值(95%CI)分别为1.50[1.12,2.02]、2.15[1.53,3.02]、1.23[1.03,1.46]和1.26[1.00,1.59](均P<0.05).apM1基因型SNP45TG和SNP276GT在两组人群中的分布没有统计学意义(P>0.05).发表偏倚分析和敏感性分析结果证实上述Meta分析结果是稳定和可靠的.结论 中国人群2型糖尿病与apM1基因SNP关系密切,SNP45G和SNP276G可能是2型糖尿病的危险因素.     

线粒体DNA ND-1基因点突变与2型糖尿病的关系

2型糖尿病患者中线粒体DNA（mtDNA)3316G→A，3316G→A，3394T→C突变频率分别为3.9%(6/152)和5.3%(8/152)，显著高于正常对照者及冠心病患者，提示mtDNA3316G→A，3394T→G突变与2型糖尿病相关。     

NLRP2基因多态性与中国汉族人群1型糖尿病的关联研究

目的探讨在中国汉族人群中核苷酸结合寡聚化结构域样受体蛋白2(NLRP2)基因的单核苷酸多态性(SNP)与经典1型糖尿病(T1DM)的相关性。方法选取就诊于中南大学湘雅二医院代谢内分泌科的510例经典T1DM患者及本地区531名无血缘关系的健康志愿者为研究对象。利用质谱法对其NLRP2基因的rs1043673位点进行基因分型。两组间一般资料的比较采用Mann-Whitney U检验和χ2检验,T1DM患者组与对照组之间基因型及等位基因频率分布的比较采用χ2检验和logistic回归分析。NLRP2多态性与各项临床特征的分析采用Kruskal-Wallis H检验。结果NLRP2基因rs1043673位点的等位基因及基因型在两组之间的分布无明显差异。在T1DM患者中,rs1043673多态性与空腹C肽(P=0.029)、餐后2 h C肽(P=0.017)以及GADA的抗体滴度(P=0.043)均有关。结论NLRP2基因的rs1043673多态性与中国汉族T1DM患者的临床特征有关。     

亚甲基四氢叶酸还原酶基因多态性与糖尿病肾病相关性研究

目的：研究亚甲基四氢叶酸还原酶（MTHFR）基因多态性与2型糖尿病肾病的关系。方法：运用聚合酶链反应－限制性片段长度多态性技术（PCR－RFLP）检测85例2型糖尿病患者（其中39例伴糖尿病肾病）及57例正常对照组MTHFR C677T基因型,采用高效液相色谱法测定血浆同型半胱酸水平。结果：糖尿病肾病组MTHFR基因TT纯合基因型,CT杂合基因型及T等位基因频率（分别为38．21％,51．28％,53．85％）均明显高于糖尿病不伴肾病组（分别为19．57％,28．26％,33．70％）及正常对照组（分别为17．54％,28．07％,31．58）,基因型和等位基因频率分布差异均有统计学意义（P＜0．05）,而MTHFR基因该多态性在不伴肾病组与正常对照组之间差异无显著性（P＞0．05）,T等位基因与糖尿病肾病的发生密切相关（OR＝2．30,95％可信区间;1．24－4．26）。糖尿病肾病组,糖尿病不伴肾病组及正常对照组中,MTHFR基因有C677T突变者血浆同型半胱氨酸水平均显著高于无基因突变者。结论：MTHFR基因C677T位碱基突变致血浆同型半胱氨酸水平高是糖尿病肾病发病的重要遗传因素。     

2型糖尿病与簇蛋白基因关联的初步研究

目的探讨2型糖尿病（T2DM）与簇蛋白（Glu）基因多态性的关联。方法聚合酶链式反应-变性梯度凝胶电泳（PCR-DGGE）和DNA测序技术分析62例T2DM患者及60例正常对照者的Glu基因外显子2和外显子5基因多态性。结果Glu基因外显子2发现1个多态位点：1963（＋A）;外显子5发现3个多态位点：（1）7476（-A）,（2）7534（-C）,（3）7521C→T。结论Glu基因外显子2和外显子5多态性在2型糖尿病组和正常对照组多态性位点基因频率分布差异有统计学意义。因此,Clu基因外显子2和外显子5多态性可能与T2DM易感性有关联。     

中国人群1型糖尿病HLA-DQ基因多态性的Meta分析

目的　综合评价中国人群HLA DQ基因多态性与 1型糖尿病 (DM)的关联性。方法　以 1型DM组和健康对照组的各HLA DQ等位基因频数(基因型频数、单倍型频数 )分布的OR值为统计量,全面检索相关文献;应用Meta分析软件包REVMAN4. 2,在基因分型水平上,对各研究的结果进行一致性检验和数据合并,并评估发表偏倚。结果　等位基因DQA1* 0301、DQA1* 0501、DQB1* 0201、DQB1* 0303、DQB1* 0401和DQB1* 0604是中国人群 1型DM的危险基因 (均P<0. 05), 他们的合并OR值分别为2. 83、2. 90、4. 17、1. 65、2. 00和 3. 00;基因型 (或单倍型 )DQA1* 0301 /DQB1* 0201、DQA1* 0301 /DQB1*0302、DQA1* 0501 /DQB1* 0201、DQA1* 0301 /DQB1* 0201 /DRB1* 0301和DQB1* 0302 /DRB1* 0405是中国人群 1型DM的危险基因型(或单倍型,均P<0. 05),他们的合并OR值分别为 8. 95、3. 09、6. 01、6. 57和 14. 85。而等位基因DQA1* 0101、DQA1* 0102、DQA1* 0103、DQA1* 0104、DQA1* 0201、DQA1* 0401、DQA1* 0601、DQB1* 0301、DQB1* 0501、DQB1* 0503、DQB1* 0601和DQB1* 0602是中国人群 1型DM的保护等位基因(均P<0. 05),他们的合并OR值分别为 0. 47、0. 38、0. 21、0. 07、0. 44、0. 39、0. 44、0. 19、0. 33、0. 32、0. 42和 0. 28; 基因型     

Inverse association between plasma homocysteine concentrations and type 2 diabetes mellitus among a middle-aged and elderly Chinese population

Background and aims

Plasma homocysteine concentrations have been reported to be associated with type 2 diabetes mellitus (T2DM) with controversial findings. The aim of the present study was to investigate the association between plasma homocysteine concentrations and T2DM.

The association studies of ADIPOQ with type 2 diabetes mellitus in Chinese populations

Adiponectin, which is secreted by the white adipose tissue, plays an important role in type 2 diabetes mellitus (T2DM) and its complications. Since 2002, many investigators explored the association between ADIPOQ single nucleotide polymorphisms and T2DM in different ethnic populations from different regions. In China, the results of numerous studies of the association between ADIPOQ and T2DM were not consistent, which may be caused by population‐specific effects or environmental effects. This review describes the association between ADIPOQ and T2DM, the metabolic characteristics and the complications of T2DM in Chinese populations. Copyright © 2012 John Wiley & Sons, Ltd.     

Association of TRB3 gene Q84R polymorphism with type 2 diabetes mellitus in Chinese population

Background TRB3, a human homolog of Drosophila Tribbles, has been shown as a critical negative regulator of Akt (also known as protein kinase B), which is a key component in insulin signaling. In addition, TRB3 is another PPAR-target gene and functions as an important link between glucose and lipid metabolism. The Q84R polymorphic variant of TRB3 has been linked to insulin resistance and related clinical outcomes. However, it is unclear whether this polymorphism is associated with type 2 diabetes mellitus (T2DM) in the Chinese population. Methods In this study, we genotyped Q84R polymorphism in 177 patients with T2DM and 245 control subjects in Chinese population by using the polymerase chain reaction/ligase detection reaction (PCR/LDR) assay. Results No significant difference in the Q84R genotype frequency was observed between T2DM patients and controls (P = 0.642). In T2DM group, the Q84R variant in cases was associated with higher FINS, higher HOMA-IR, and lower LnISI (P = 0.003, 0.001, and 0.001, respectively). However, the changes in HOMA-IR and LnISI were not significant in controls (the P value is 0.098 and 0.203, respectively). In addition, FINS levels were also significantly increased from Q84Q to R84 in controls (P = 0.036). Conclusion Our data indicate that the TRB3 Q84R polymorphism is not associated with T2DM in Chinese population. However, the Q84R variant is associated with insulin resistance among T2DM patients in Chinese population.     

载脂蛋白J基因多态性与2型糖尿病相关性分析

目的探讨载脂蛋白J(ApoJ)外显子3、4、7、8基因多态性与2型糖尿病(T2DM)的关系。方法2002-11~2003-06对贵阳医学院附属医院,利用聚合酶链式反应-变性梯度凝胶电泳技术(PCR-DGGE)对61例T2DM患者、60例正常对照者的ApoJ外显子3、4、7、8基因进行基因筛查,并对异常条带进行测序分析。结果我国ApoJ基因外显子7缺失与插入(DVSI)基因型在T2DM与正常对照组间分布差异显著(P<0.01),ApoJ外显子3、4、8差异无显著性(P>0.05)。结论我国2型糖尿病患者ApoJ外显子7基因插入与缺失多态性可能与2型糖尿病发病有关联,是2型糖尿病的危险因素之一。     

中国人群2型糖尿病患者付氧酶基因多态性与冠心病关系的研究

探讨中国２型糖尿病患者付氧酶（ＰＯＮ）基因与并发冠心病（ＣＡＤ）的关系。方法利用聚合酶链反应一变性梯度凝胶电泳技术对４９例２型糖尿病合并ＣＡＤ患者,４９例未合并ＣＡＤ的２型糖尿病对照者和１０１例健康对照者进行ＰＯＮ基因外显子筛查。结果发现中国人群ＰＯＮ基因第１９１位密码子存在Ｇｌｎ＾１９１－Ａｒｇ多态性,等位基因以Ａ／Ｂ表示。ＣＡＤ患者ＰＯＮ基因的３种基因型（ＡＡ、ＡＢ和ＢＢ）的构成比与２型糖尿病     

中国汉族人群Calpain-10基因UCSNP43多态性与2型糖尿病相关性的meta分析

对中国汉族人群Calpain-10基因UCSNP43位点多态性与2型糖尿病的相关性进行meta分析.Calpain-10基因UCSNP43位点G等位基因、GG基因型可能是中国汉族人群2型糖尿病的危险因子;A等位基因、GA基因型可能为保护因子.     

中国汉族人群Calpain-10基因UCSNP43多态性与2型糖尿病相关性的meta分析

对中国汉族人群Calpain-10基因UCSNP43位点多态性与2型糖尿病的相关性进行meta分析.Calpain-10基因UCSNP43位点G等位基因、GG基因型可能是中国汉族人群2型糖尿病的危险因子;A等位基因、GA基因型可能为保护因子.     

中国汉族人群Calpain-10基因UCSNP43多态性与2型糖尿病相关性的meta分析

对中国汉族人群Calpain-10基因UCSNP43位点多态性与2型糖尿病的相关性进行meta分析.Calpain-10基因UCSNP43位点G等位基因、GG基因型可能是中国汉族人群2型糖尿病的危险因子;A等位基因、GA基因型可能为保护因子.     

线粒体DNA变异与老年2型糖尿病患者易感性的相关性

目的 研究湖北地区老年2型糖尿病(T2DM)患者中线粒体基因突变的发生率及其相关性.方法 采用PCR-RFLP、基因测序技术,对175例老年T2DM患者和200例糖耐量正常的健康老年对照组进行检测.结果 MIND1 3316(G→A)、MTTL1 3243(A→G)、MIND13394( T→C)、MIND14216(T→C) MIND14164(A→G)和MIND2 5178( T→C)变异率分别为3.26％、2.72％、1.71％、4％、34.9％;对照组检出3316(G→A)突变2例(0.99％)、4164 5例(0.99％)、5718(T→C)变异64例(32.3％),未检出3394、4216的点突变;两组间3394(T→C)变异率差别有统计学意义(P＜0.05);且T2DM组5178A基因型血清TC水平低于5178C基因型(P＜0.05),但TG、LDL-C、HDL-C、apoA、apoB、Lp(a)水平两组无统计学意义.结论 3394( T→C)与老年T2DM患者的易感性有一定关联,5178(T→C)变异与湖北地区老年汉族人T2DM的脂代谢相关.     

中国汉族人群2型糖尿病与脂联素基因SNP-11377位点相关性的Meta分析

目的评价脂联素基因SNP-11377位点与T2DM的相关性。方法采用Meta分析评估SNP-11377位点与T2DM的相关性。异质性检验后采用M-H固定效应模型合并比值比(OR)值,并进行发表偏倚检验。结果 (1)共纳入10篇文献,其中病例组2831例、对照组3035例。(2)异质性检验显示,脂联素基因SNP-11377在各研究间是同质(I2=11.2%,P>0.05),各研究之间不存在异质性。(3)M-H固定效应模型进行数据合并,结果显示合并OR为1.09(95%CI为1.00～1.18,P=0.05)。(4)Begg和Egger偏倚分析均显示无明显发表偏倚。结论脂联素基因SNP-11377G等位基因可能与中国汉族人群T2DM的发病风险相关。     

中国汉族人群脂联素+276位点基因多态性与2型糖尿病相关性的meta分析

目的通过meta分析评估中国汉族人群脂联素基因(adiponectin,ADIPOQ)+276G/T(rs1501299)位点单核苷酸多态性与2型糖尿病(T2DM)的相关性。方法检索自2000年1月1日至2018年12月31日PubMed、Ovid、CBM、Springer、CNKI和WanFang Data中关于中国汉族人群脂联素基因rs1501299(+276G/T)与2型糖尿病相关性的病例-对照研究,并辅以文献追溯。采用Review Manager 5.3软件进行meta分析。结果共纳入13项研究,其中T2DM患者3 384例,健康对照者3 187例。meta分析结果显示,在隐性遗传模式下,两组差异有统计学意义[OR=1.29,95%CI(1.13, 1.49),P<0.05]。该位点基因多态性meta分析结果发表偏倚较小,研究纳入的样本量大、精度较高,所有研究组都具有较好代表性。结论中国汉族人群脂联素基因+276G/T位点基因多态性与2型糖尿病可能具有相关性。