RBP4与FOXO1基因单核苷酸多态性与2型糖尿病的相关性研究

目的 探讨视黄醛结合蛋白(RBP4)基因、叉头框因子-1(FOXO1)基因单核苷酸多态性(SNPs)在中国汉族人群中的频率分布及其与2型糖尿病(T2DM)的相关性.方法 采用TaqMan探针基因分型技术结合琼脂糖凝胶电泳技术,检测384例T2DM患者和384例健康者RBP4、FOXO1共10个SNP位点的基因型及等位基因频率分布,同时测定其空腹血糖(FBG)、总胆固醇(TC)、三酰甘油(TG)水平.结果 T2DM组RBP4-803,G>A;+5169,C>T;+6969,G>C 3个SNP位点的基因型频率和等位基因频率分布与对照组比较差异无统计学意义(P>0.05).经logistic回归分析,各位点均未发现与T2DM有关的基因型.单倍体表型分析也未发现与T2DM有关的单倍型.FOXO1的7个SNP位点检测结果显示,rs7324943 G/T的等位基因频率与基因型频宰在T2DM组和对照组间差异均有统计学意义(χ~2=4.02,P=0.044).分层分析显示,在年龄40岁和非高血压的人群中,GT基因型患T2DM的风险较GG纯合子高比值比(OR)分别为1.47,1.80].T等位基因携带者患T2DM的风险较非T等位基因携带者高(OR分别为1.42,1.79).两组间rs17592236 C/T的等位基因频率和基因型频率(χ~2=0.39,P=0.401),差异均无统计学意义,但分层分析发现,在年龄≤40岁的人群中,CT与TT基因型患T2DM风险较CC纯合子高(OR分别为6.33,10.15),T等位基因携带者患T2DM风险较非T等位基因携带者高(OR=7.11).单倍体表型分析结果显示,单倍型CT可使T2DM患病风险下降约28%.结论 中国汉族人群RBP4-803,G>A;+5169,C>T;+6969,G>C的3个SNP位点与T2DM发病风险无关.FOXO1的rs7324943 G/T、rs17592236 C/T和单倍型CT与中国汉族人群T2DM发病风险有关,但其作用机制需深入研究.

Association study between single nucleotide polymorphisms on retinol binding protein 4,FOXO1 and type 2 diabetes mellitus

Objective To investigate the distribution of single nucleotide polymorphisms(SNPs) on retinol binding protein 4(RBP4) genes and forkhead box O1 (FOXO1) gene, and their relationships with the occurrence of type Ⅱ diabetes mellitus (T2DM) in Chinese Han population. Methods Totally ten SNPs on RBP4 and FOXO1 were determined in 384 T2DM patients and 384 normal controls by TaqMan probe genotyping and agarose gel electrophoresis methods. And their serum level of fasting blood glucose (FBG), total cholesterol (TC) and trigly- ceride (TG) were also estimated. Results For RBP4, there was no significance for various genetypes and alleles including - 803 G > A, + 5169 C > T, and + 6969 G > C between two groups (P > 0.05). Each genotype had no relationships with T2DM (using adjusted logistic regression models). No haplotype was associated with T2DM. For FOXO1, among seven SNPs typed, significant variation was found in the frequency distribution of rs7324943 G/T in the two groups(χ~2=4.02, P = 0.044), and further stratification analysis showed that in subjects of aged 40 and non-hypertension, there was a higher risk of T2DM in GT heterozygous carriers than in GG homozygous carriers (OR = 1.47, 1.80), T allele carriers showed higher risk than non-T carriers (OR = 1.42,1.79). For rs17592236 C/T, though no significant frequency variation was found between two groups (χ~2 = 0.39, P = 0.401), but in subjects of aged ≤ 40, stratification analysis showed dramatically increased risk of T2DM in CT and TT carriers than in CC carriers (OR = 6.33,10.15), T allele carriers showed 7. 11-fold higher risk than non-T carriers. A haplotype CT related to T2DM susceptibility was also found, which could decrease the risk of its carriers by 28%. Conclusions For BBP4, the polymorphisms of - 803 G > A, + 5169 C > T, and + 6969 G > C had no relationships with T2DM in Chinese Han population. For FOXO1, the polymorphism of rs7324943 G/T,rs17592236 C/T and a haplotype CT were found related to the susceptibility of T2DM in Chinese Han population. Yet further studies are necessary to explain the impact of these polymorphisms on the disease occurrence.