妊娠期糖尿病患者核苷酸焦磷酸酶/磷酸二酯酶1基因多态性研究

Association of ENPP1 polymorphisms with gestational diabetes mellitus

目的了解妊娠期糖尿病(GDM)患者核苷酸焦磷酸酶/磷酸二酯酶1(ENPP1)基因位点rs1044498 K121Q,rs7754561 A>G+1044TGA和rs1799774 IVS20deIT-1 1多态性的分布情况。方法选取94例GDM患者(GDM组)与94例健康孕妇(对照组)。采用聚合酶链反应-高分辨率溶解曲线(PCR-HRM)技术检测ENPP1基因位点rs1044498 K121Q,rs7754561 A>G+1044 TGA和rs1799774 IVS20de1T-1 1的3个基因型。样本的群体代表性进行哈丁温伯格遗传平衡(HWE)检验;组间基因型频率比较采用SPSS 20.0软件进行x^2检验,连锁不平衡采用SHEsis软件进行分析。结果 rs1044498的C等位基因在GDM组的频率为68.1%高于对照组的12.2%,差异有统计学意义(P<0.01);CC、AC基因型携带者患GDM的风险分别是AA基因型携带者的90.46和2.339倍。rs7754561的A等位基因在GDM组的频率为43.1%高于对照组的32.4%,差异有统计学意义(P<0.05);AA、AG基因型携带者患GDM的风险分别是GG基因型携带者的3.576和0.445倍。rs1799774等位基因频率分布差异无统计学意义,-I-基因型携带者患GDM的风险是TT型携带者的3.084倍,是Tdel+TT携带者的3.478倍。单倍型AAT、ACdel、GAT、GCT、ACT与GDM发病正相关(OR>1)。结论 rs1044498 K121Q和rs7754561 A>G+1044TGA位点的基因多态性与GDM有关,rs1044498 C等位基因和rs7754561 A等位基因可能是导致GDM发病的高危因素。

Objective To investigate the association of ectonucleotide pyrophosphatase/ phosphodiesterase 1 （ENPP1） gene polymorphisms with the risk of gestational diabetes mel itus （GDM）. Methods The polymorphisms of ENPP1 （rs1044498 K121Q, rs7754561 A＆gt;G＋1044TGA, rs1799774 IVS20delT- 11） were genotyped by polymerase chain reaction- high resolution melt（PCR- HRM） method in 94 GDM women and 94 healthy pregnant women（control group）. Hardy- Weinberg equilibrium （HWE） test was used to evaluate the representative of the sample. Genotype frequencies between groups were compared with Chi- square test, SPSS 20.0. Linkage disequilibrium was tested using SHEsis. Results The C al ele of rs1044498 was signifi-cantly higher in GDM group than that in control group （0.681 vs. 0.122, P〈0.01）. Compared with AA, the CC and AC genotype carriers had 90.46 and 2.339 times more susceptibility to GDM. The A al ele of rs7754561 was higher in GDM group than that of control group （0.431 vs. 0.324, P〈0.05）. Compared with GG, the AA and AG genotype carriers had 3.576 and 0.445 times more susceptibility to GDM. However, as for rs1799774, no significant difference was found in the distribution of the al eles between two groups,- ｜- genotype carriers were 3.084 times more susceptibility to GDM than TT carriers, and 3.478 times than TT＋Tdel carri-ers. In addition, the AAT, ACdel, GAT, GCT, ACT haplotypes might contribute to susceptibility to GDM. Conclusion The poly-morphisms of ENPP1 genes rs1044498 and rs7754561 are likely to associated with GDM, the C al ele of rs1044498 and A al ele of rs7754561 may be risk factors for GDM.