KCNQ1基因单核苷酸多态性与妊娠期糖尿病相关性研究

目的探讨KCNQ1基因单核苷酸多态性(SNP)位点rs2237892、rs2237895及rs2237896与妊娠期糖尿病(GDM)的相关性。方法本研究共纳入1436例孕妇,其中GDM 520例,糖耐量正常(NGT) 641例以及50 g葡萄糖激发试验阴性GCT(-)]275例,后两组设为对照。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)的方法检测KCNQ1基因的多态性。并以稳态模型评估指数(HOMA)评估其胰岛β细胞功能及胰岛素抵抗。结果(1)SNP rs2237896的三种基因型(AA、AG、GG)在GDM组及对照组分布频率分别为8.8%、46.7%、44.4%和13.1%、47.5%、39.4%,两组的基因型分布频率差异显著(P=0.011)。该位点在其隐性模型中(AA vs AG+GG),两组差异仍显著(P=0.016)。rs2237896等位基因A、G的分布频率在GDM组和对照组分别为32.2%、67.8%和36.8%、63.2%,GDM组中G等位基因分布频率高于对照组,差异有显著性P=0.012,OR 1.228(95%CI 1.045～1.442)]。(2) SNP rs2237895的三种基因型(AA、AC、CC)在GDM组及对照组分布频率分别为39%、53.3%、7.7%和48.1%、43.0%、8.8%,两组的基因型分布频率差异显著(P=0.022)。该位点在其显性模型中(CC+AC vs AA),两组差异仍显著(P=0.001)。其等位基因A、C的分布频率在GDM组和对照组分别为65.7%、34.3%和69.7%、30.3%,GDM组中C等位基因分布频率高于对照组,差异有显著性P=0.028,OR 1.200(1.020～1.411)]。(3)将受试者按SNP rs2237895基因型AA、AC、CC分类,其HOMA-B值分别为(158.15±99.66)、(141.72±132.62)和(131.54±189.85),差异具有显著性(P=0.021),基因型CC的孕妇具有最小的HOMA-B值。同时,该位点在显性模型中,差异也有显著性(P=0.005)HOMA-B值为(140.25±142.15)(AC+CC)vs(158.15±99.66)(AA)]。结论在中国人群中KCNQ1基因SNP与GDM具有一定相关性,可能与具有风险基因的个体其胰岛β细胞功能更易受到损伤有关。

Association of KCNQ1 gene single nucleotide polymorphism with gestational diabetes mellitus

Objective： To investigate the association of three single nucleotide polymorphisms（SNPs） including rs2237892, rs2237895 and rs2237896 in KCNQ1 gene with gestational diabetes mellitus（GDM）. Methods： A total of 1,436 pregnant women were recruited in our study： 520 with GDM, 641 with normal glucose tolerance（NGT） and 275 with negative result of 50 g glucose challenge test GCT（-）7, and the latter two groups as controls. Three SNPs in KCNQ1 gene were examined in all participants by using a polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP） method. The homeostasis model assessment index（HOMA） was calculated to assess the function of beta cell and insulin resistance.
Results： （1） The AA, AG significantly between GDM group and GG genotype frequencies of and controls （8. 8%, 46.7% and SNP rs2237896 variant dittered 44.4% vs. 13.1%, 47.5% and 39.4%, P=0. 001）. Under its recessive model（AA vs. AG＋GG）, the association remained positively （P=0. 016）. The G-allele was associated with an increased risk of GDM OR 1. 228（1. 075-1. 529）, P=0. 006]. （2） The AA, AC and CC genotype frequencies of SNP rs2237895 variant differed obviously betweenGDM group and eontrols（39%, 53.3%and 7.7% vs. 48.1%, 43.0% and 8.8%）. Using its dominant model（CC＋AC vs. AA）, the association was also significant（P=0. 001）. In addition, a positive association was found between the C-allele in rs2237895 and GDM P=0. 028, OR 1. 200（1. 020- 1.411）]. （3） Among all participants, the HOMA-B value differed significantly in AA, AC and CC genotypes of SNP rs2237895 （158. 15 ±99.66, 141.72± 132.62 and 131.54 ±189.85, respectively, P= 0. 021） and the pregnant women with CC-genotype had the lowest HOMA-B value. And using the dominant model, the association was significant（P=0. 005） EHOMA-B was（140. 25±142.15）（AC＋kCC） vs. （158. 15±99.66） （AA）].
Conclusions： KCNQ1 gene polymorphisms are associated with an increased risk of GDM in a Chinese population.