编码TAFI505A/G和1040C/T基因多态性与2型糖尿病关系的研究

Study on relationship between polymorphisms of thrombin activatable fibrinolysis inhibitor and risk of type 2 diabetes mellitus

目的:探讨凝血酶激活的纤溶抑制物(TAFI)编码区2个位点(505A/G,1040C/T)的单核苷酸多态性与2型糖尿病(T2DM)发病及病程进展的相关性。方法:应用聚合酶链反应-限制性内切酶片段长度多态性(PCR-RFLP)分析技术检测267例T2DM患者(单纯糖尿病110例,早期糖尿病肾病90例,临床糖尿病肾病67例)和140例正常对照者的TAFI505A/G、1040C/T2位点的多态性。结果:505A/G多态性位点病例组与对照组中各基因型的分布差异无统计学意义。在1040C/T位点,T2DM组T等位基因的频率与对照组相比明显下降(15.6%对25.7%,P<0.05),其T/T纯合子型比例亦显著下降(P<0.05,95% OR 0.28,CI0.11～0.70)。但这种显著性差异只在早期糖尿病肾病患者中表现出来,随着病情的进展,这种差异在临床糖尿病肾病患者组与对照组间却表现不明显,差异无统计学意义(P>0.05)。结论:1040C/T多态性位点T等位基因可能作为一种保护性基因在T2DM发病及早期病情进展中起到保护性作用,即TAFI1040C/T基因多态性可能与T2DM患病危险度存在关联。

Objective：To investigate the possible association of two polymorphisms（505 A/G,1040 C/T）related to the thrombin activated fibrinolysis inhibitor（TAFI）activity with increased risk of type 2 diabetes mellitus （T2 DM）.Method：The two allele frequencies of the 505 A/G and 1040 C/T polymorphisms which resulted in two amino acid substitutions were studied：Ala for Thr at position 147 and Ile for Thr at position 325 in 267T2 DM patients and 140 healthy controls matched by age,gender,ethnicity and body mass index （BMI）,using polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） typing analysis.Result：No significant differences of TAFI levels appeared between patients and controls at 505 A/G.At 1040 C/T,the detected frequency for the T allele in the T2 DM group was significantly smaller than that of the control group（15.6% versus 25.7%,respectively;P0.05）.This difference was due to the relative decrease of T/T homozygotes in the group of patients,in comparison to controls（P0.05,95% OR 0.28,CI 0.11-0.70）.The same pattern of significance was also observed between controls and the subgroups of patients with initial stages of T2 DM categorized by the urinary albumin excretion rate（UAER）.Conclusion：At 1040 C/T the frequency for the T allele could be strongly associated with increased risk for T2 DM in a subset of the general population,implying that the T allele may confer protection against the onset of T2 DM only in homozygosity,which function may be as a recessive trait.