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.     

Calpain10基因多态性与维吾尔族2型糖尿病患者亲级关系的研究

目的 分析Calpain10基因UCSNP43和UCSNP44位点多态性与新疆维吾尔族2型糖尿病家系中小同亲级的相关性.方法 以新疆62个维吾尔族2型糖尿病核心家系为样本,采用PPAP(population and pedigree analysis programs)统计软件和Penrose法来研究其遗传方式;将75个新疆维吾尔族2型糖尿病家系一级亲和二级亲成员481人做两组比较分析,采用基因芯片方法 榆测UCSNP43和UCSNP44位点多态性,应用SPSS 13.0统计软件分析Calpain10基凶多态性是否在2型糖球病家系不同亲级关系存在差异.结果 (1)2型糖尿病家系一级亲的遗传度为0.578,二级关的遗传度为0.032;(2)一级和二级亲属之间Calpain10基因UCSNP43、UCSNP44基因型和等位基因频率分布差异均无统汁学意义(P<0.05);(3)Calpain10其因UCSNP43位点AA基因型携带者体重指数、空腹胰岛素水平较GG和GA基因型携带者高(P<0.05或P<0.01).结论 新疆维吾尔族2型精尿病的遗传度随着亲缘系数的降低析减小;UCSNP43位点AA基因携带者胰岛素抵抗程度较GG和AG型携带者高.     

陕西地区汉族2型糖尿病患者Calpain-10基因多态性与冠状动脉粥样硬化性心脏病易感性的相关性分析

目的探讨陕西地区汉族T2DM患者中Calpain-10基因多态性与冠状动脉粥样硬化性心脏病(CHD)易感性的相关性。方法选取2016年1月至2018年12月于宝鸡市人民医院行冠状动脉造影检查的T2DM患者669例,根据造影结果分为T2DM合并CHD组(CHD)415例和无CHD组(T2DM)254例。同期选取300名行冠状动脉造影检查排除CHD的非T2DM患者作为对照组(Con),采用聚合酶链反应-限制性内切酶分析法检测所有研究对象Calpain-10基因SNP43位点基因型。结果 Con、T2DM组SNP43位点等位基因分布频率比较,差异有统计学意义(P0. 05);Con、CHD组SNP43位点基因型和等位基因分布频率比较,差异有统计学意义(P0. 05);CHD、T2DM组SNP43位点基因型和等位基因分布频率比较,差异有统计学意义(P0. 05)。二元逐步回归分析结果显示,Calpain-10基因SNP43位点G等位基因是T2DM患者发生CHD的影响因素(OR 1. 725,95%CI 1. 027～2. 899,P=0. 007)。结论陕西地区汉族T2DM患者Calpain-10基因SNP43位点多态性可能与CHD易感性相关。     

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.     

脂联素基因启动子区-11377 C/G多态性与2型糖尿病及糖尿病肾病的关系

目的探讨桂北地区汉族人群脂联素基因启动子区-11377 C/G单核苷酸多态性各基因型及等位基因频率分布,分析其与2型糖尿病（T2DM）及糖尿病肾病（DN）的关系。方法采用PCR-RFLP技术检测100例健康对照者及232例T2DM患者（其中DN 105例）的脂联素基因-11377 C/G位点基因型及等位基因频率分布。结果 T2DM患者脂联素基因启动子区-11377的GG基因型频率和G等位基因频率高于健康对照者（P〈0.05,Or=1.625,95%CI 1.05～2.51）;脂联素基因启动子区-11377基因型及等位基因频率分布在T2DM、DN患者间无统计学意义;T2DM患者CG＋GG基因型BMI高于CC基因型（P〈0.05）。结论脂联素基因启动子区-11377 C/G与桂北地区汉族人群T2DM发病有相关性,G等位基因可能是T2DM发病的遗传易感基因。     

胰十二指肠同源异型盒基因-1多态性与2型糖尿病的相关性

目的探讨胰十二指肠同源异型盒基因(PDX)-1多态性位点(rs4415872,rs1124607和rs4581569)与上海汉族人群2型糖尿病的关系。方法选取1 285例正常健康个体为对照组,经确诊的1 245例2型糖尿病患者为病例组。收集静脉血液标本1 ml,提取全基因组DNA。应用Taqman基因分型技术进行多态性检测。结果与对照组相比,PDX-1基因rs1124607位点的基因型和等位基因频率分布在病例组中具有统计学意义[基因型:P=7.82×10~(-5);等位基因:P=0.000 9,OR=0.780(0.688~0.886)]经Bonferroni矫正后仍具有统计学差异(基因型:P=2.35×10~(-4);等位基因:P=0.000 3)。结论 PDX1基因rs1124607位点可能与上海汉族人群2型糖尿病具有相关性。     

Calpain-10基因SNP43单核苷酸多态性与2型糖尿病的相关性研究

采用错配聚合酶链反应技术,对128例2型糖尿病患者(T2DM组)和102例健康者(对照组)的Cal-pain-10基因SNP43单核苷酸多态性进行基因分型,并测定其体质量指数(BMI)、腰围/臀围、空腹血糖、甘油三酯和胆固醇.结果显示,两组Capain-10基因SNP43等位基因G、A频率无统计学差异(P>0.05);两组Calpain-10基因SNP43多态性中,GG型与GA AA型基因者的上述指标比较均无统计学差异(P均>0.05);对照组基因GA AA型者的甘油三酯较GG型者高(P<0.05).认为Calpain-10基因SNP43单核苷酸多态性可能与T2DM的遗传易感性无相关性.     

山东省汉族人群MGEA5、GFPT2基因多态性与2型糖尿病关联性研究

目的 研究MGEA5与GFPT2基因单核苷酸多态性与山东省汉族人群2型糖尿病的相关性.方法 用酚/氯仿法提取外周血DNA行PCR扩增,扩增产物用1.5%琼脂糖电泳,目的 条带直接测序.结果 MGEA5基因SNP5-14位点等位基因为A/T,DM组T等位基因频率较正常对照(NC)组显著升高(P<0.01),基因型AT/TT的DM患者较AA基因型DM患者具有较高的FIns、2hIns、FC P、2hC P水平,而ISI显著降低(P<0.05).GFPT2基因SNP7位点等位基因为C/T,DM组T等位基因频率较NC组显著升高(P<0.01),基因型CT/TT的DM患者较CC基因型DM患者具有较高的FIns、2hIns、FC P、2hC P水平,而ISI显著降低(P<0.01).结论 MGEA5-14和GFPT2-7等位基因可能是山东汉族2型糖尿病的主要易感基因位点.     

钙蛋白酶10基因多态性与高血压家族史及血糖水平的关联

目的　分析高血压家系和非高血压家系后代 ,钙蛋白酶 10 (CAPN 10 )基因多态性与高血压家族史、血糖水平的关联。方法　测定大庆地区 187个高血压家系和 191个非高血压家系第二代直系亲属的空腹血糖、胰岛素、甘油三酯和纤维蛋白原 ,用聚合酶链反应 (PCR)单链构型多态法(SSCP) ,DNA测序分析CAPN 10基因多态性。结果　 (1)高血压及非高血压家系的第二代直系亲属中CAPN 10基因UCSNP 4 3G/G型频率分别为 86 6 %、75 4 % (P <0 0 5 ) ;该基因型携带者在有高血压家族史有高血压人群明显多于无高血压家族史非高血压人群 (OR为 2 84 ,P =0 0 1)。 (2 )多因素分析 ,排除年龄、性别和体重指数影响后 ,空腹血糖最高四分变量组 (5 4 2± 0 1)mmol/L比最低四分变量组(4 0 9± 0 3)mmol/L携带该基因型明显增多 (OR值为 3 32 )。结论　CAPN 10基因UCSNP 4 3可能是大庆地区原发性高血压和糖尿病的遗传因素之一 ,其中G/G型对于预测高血压患者后代是否发生 2型糖尿病有一定作用     

Association of calpain-10 polymorphisms with type 2 diabetes in the Tunisian population

BACKGROUND: Genome-wide analyses of the genetic predisposition to type 2 diabetes mellitus (T2DM) in different isolates and populations have identified regions of interest called non insulin-dependent diabetes mellitus (NIDDM) 1, 2, 3 and 4. At the NIDDM1 locus (2q37.3), calpain-10 (CAPN10) encodes for a ubiquitously expressed protease implicated in the two fundamental pathophysiological aspects of T2DM. This is a report of the results of a study of the association of four CAPN10 polymorphisms with T2DM in the Tunisian population. PARTICIPANTS AND METHODS: A total of 222 T2DM patients with a diabetes duration of 10 years or more and 206 healthy controls were enrolled to analyze the frequency distribution of four CAPN10 polymorphisms (UCSNP-43, UCSNP-19, UCSNP-110 and UCSNP-63) using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in the Tunisian population. We also investigated the association of T2DM with different haplotypes and haplotype combinations. RESULTS: Only the A allele of UCSNP-43 showed an association with T2DM (odds ratio, OR=1.86). We also identified a novel combination of haplotypes (121/221) defined by three polymorphisms (UCNSP-43, -19 and -63) that is associated with an increased risk of T2DM (OR=2.38). CONCLUSION: In this study involving the Tunisian population, we identified genetic variants within CAPN10 that are linked with T2DM and a novel haplotype combination, 121/221, associated with an increased susceptibility to T2DM.     

Protein kinase C／ζ （PRKCZ） Gene is associated with type 2 diabetes in Han population of North China and analysis of its haplotypes

AIM: To identify the susceptible gene (s) for type 2 diabetes in the prevousely mapped region, lp36.33-p36.23, in Han population of North China using single nucleotide polymorphisms (SNPs) and to analyze the haplotypes of the gene (s) related to type 2 diabetes.METHODS: Twenty three SNPs located in 10 candidate genes in the mapped region were chosen from public SNP domains with bioinformatic methods, and the single base extension (SBE) method was used to genotype the loci for 192 sporadic type 2 diabetes patients and 172 normal individuals, all with Han ethical origin, to perform this case-control study. The haplotypes with significant difference in the gene (s) were further analyzed.RESULTS: Among the 23 SNPs, 8 were found to be common in Chinese Han population. Allele frequency of one SNP,rs436045 in the protein kinase C/ζ gene (PRKCZ) was statistically different between the case and control groups (P&lt;0.05). Furbhennore, haplotypes at five SNP sites of PRKCZ gene were identified.CONCLUSION: PRKCZgene may be associated with type 2 diabetes in Han population in North China. The haplotypes at five SNP sites in this gene may be responsible for this association.     

Variants within the calpain-10 gene and relationships with type 2 diabetes (T2DM) and T2DM-related traits among Tunisian Arabs

BackgroundCommon variations in the calpain 10 (CAPN10) gene variants UCSNP-43, UCSNP-19 and UCSNP-63, and the 112/121 diplotype, are associated with an increased risk of type 2 diabetes (T2DM) and T2DM-related traits.MethodsThe association of UCSNP-43, -19 and -63 CAPN10 SNPs with T2DM was assessed in 917 Tunisian T2DM patients and 748 ethnically matched non-diabetic controls. CAPN10 genotyping was done by PCR-RFLP.ResultsSignificant differences in UCSNP-19 MAF, but not UCSNP-43 or -63, and genotype distribution were seen between patients and controls. Heterogeneity in UCSNP-19, but not UCSNP-43 and -63, genotype distribution was noted according to geographical origin. Obesity was associated with UCSNP-19, while raised fasting glucose was associated with UCSNP-63, and increased HDL was associated with UCSNP-43. Enrichment of homozygous UCSNP-19 2/2 was seen in overweight and obese compared with lean patients; logistic-regression analyses demonstrated a positive association of the 2/2 genotype with overweight [P = 0.003; OR (95% CI) = 2.07 (1.28–3.33)] and obese [P = 0.021; OR (95% CI) = 1.83 (1.10–3.07)] patients. Of the six CAPN10 haplotypes identified, significant enrichment of only haplotype 111 was seen in T2DM patients [Pc = 0.034; OR (95% CI) = 1.22 (1.06–1.41)], while the frequency of all identified CAPN10 diplotypes, including the high-risk 112/121, was comparable between patients and controls.ConclusionWhile CAPN10 UCSNP-19 SNP and haplotype 111 contribute to the risk of T2DM in Tunisian subjects, no significant association between CAPN10 diplotypes and T2DM was demonstrated.     

Protein kinase C/ζ(PRKCZ) Gene is associated with type 2 diabetes in Han population of North China and analysis of its haplotypes

AIM: To identify the susceptible gene (s) for type 2 diabetes in the prevousely mapped region, 1p36.33-p36.23, in Han population of North China using single nucleotide polymorphisms (SNPs) and to analyze the haplotypes of the gene (s) related to type 2 diabetes.METHODS: Twenty three SNPs located in 10 candidate genes in the mapped region were chosen from public SNP domains with bioinformatic methods, and the single base extension (SBE) method was used to genotype the loci for 192 sporadic type 2 diabetes patients and 172 normal individuals, all with Hah ethical origin, to perform this casecontrol study. The haplotypes with significant difference in the gene (s) were further analyzed.RFSULTS: Among the 23 SNPs, 8 were found to be common in Chinese Han population. Allele frequency of one SNP,rs436045 in the protein kinase C/ζgene (PRKCZ) was statistically different between the case and control groups (P＜0.05). Furthermore, haplotypes at five SNP sites of PRKCZ gene were identified.CONCLUSION: PRKCZgene may be associated with type 2 diabetes in Hah population in North China. The haplotypes at five SNP sites in this gene may be responsible for this association.     

CAPN10基因变异与中国北方汉族人群血脂水平的关联研究

目的探讨CAPN10基因变异与中国北方汉族人群血脂水平的关系。方法研究选择427例2型糖尿病合并高血压个体以及547例年龄、性别相匹配的正常对照。所有个体均为中国北方汉族人,均未服用调脂药物。应用多聚酶链式反应-限制性片段长度多态性的方法对CAPN10基因的SNP-44、43、19、63多态进行基因型鉴定。结果应用线性回归模型校正年龄、性别和体重指数的作用,比较不同基因型和双体型个体的血脂水平差异。在病例组中,甘油三酯（TG）水平在SNP-63 CC纯合子个体和T等位基因携带者中有边缘性差异（P=0.05）。在对照组中,SNP-19多态11纯合子个体的TG水平高于等位基因2的携带者,但未达到统计学显著性（P=0.06）,而SNP-63 T等位基因亦有增高对照个体的TG水平的倾向,但在加性、显性和隐性模型中均未达到统计学显著性（P值分别为0.07,0.07和0.06）。在病例组和对照组中6种常见双体型个体的血脂水平均无统计学差异。结论CAPN10基因多态可能不是我国北方汉族人群血脂异常的主要危险因素。     

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.     

Calpain 10 gene polymorphisms are related, not to type 2 diabetes, but to increased serum cholesterol in Japanese

A G-to-A (UCSNP-43) polymorphism of the calpain-10 gene was significantly associated with type 2 diabetes (DM) in Mexican-American, and was postulated, together with a T-to-C (UCSNP-44) polymorphism, as a risk factor for DM. We examined the association of these genotypes with DM in Japanese. Eighty-one subjects with DM and 81 non-diabetic subjects (NGT) were recruited. The number of subjects with genotypes UCSNP-43 G/G, G/A and A/A were 76, 5 and 0, respectively, for the DM and NGT groups. The number of subjects with genotypes UCSNP-44 T/T, T/C and C/C were 66, 14 and 1 for the DM group and 64, 17 and 0 for the NGT group. There was no difference between the groups in terms of frequency of any genotype combinations. No association between the genotypes and DM was observed. We next examined the differences between the genotypes or genotype combinations in terms of the traits related to DM, obesity, hypertension and dyslipidemia. No differences were observed between the genotypes UCSNP43 G/G and G/A, between UCSNP-44 T/T and the others, or between the genotype combination UCSNP-43 G/G and UCSNP-44 T/T and the others, except that the individuals with the genotype combination had significantly increased serum cholesterol levels (212.6 +/- 34.3 vs. 198.5 +/- 29.9, P=0.020). The genotype combination might be a risk factor, not for DM, obesity and hypertension, but for increased serum cholesterol.