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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。
Objective To investigate the association of SNP rs2237892, rs2237895 and rs2237896 with gestational diabetes mellitus (GDM) in KCNQ1 gene. METHODS: A total of 1,436 pregnant women were enrolled in this study. Among them, 520 were GDM, 641 with normal glucose tolerance (NGT), and 275 were negative with 50 g glucose challenge [GCT (-)]. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to detect KCNQ1 gene polymorphism. The steady-state model assessment index (HOMA) was used to evaluate the islet β-cell function and insulin resistance. Results (1) The distribution frequencies of three genotypes (AA, AG, GG) of SNP rs2237896 in GDM group and control group were 8.8%, 46.7%, 44.4% and 13.1%, 47.5% and 39.4% Type distribution frequency difference was significant (P = 0.011). The locus was significant in both groups (P = 0.016) in its recessive model (AA vs AG + GG). The distribution frequency of rs2237896 allele A and G was 32.2%, 67.8% and 36.8%, 63.2% respectively in GDM group and control group, and the distribution frequency of G allele in GDM group was higher than that in control group [P = 0.012, OR 1.228 (95% CI 1.045 ~ 1.442)]. (2) The frequencies of three genotypes (AA, AC, CC) of SNP rs2237895 in GDM group and control group were 39%, 53.3%, 7.7% and 48.1%, 43.0% and 8.8% Distribution frequency difference was significant (P = 0.022). The locus was significantly different between the two groups (P = 0.001) in its dominant model (CC + AC vs AA). The distribution frequency of allele A and C was 65.7%, 34.3% and 69.7%, 30.3% in GDM group and control group, respectively. The distribution frequency of C allele in GDM group was higher than that in control group [P = 0.028, OR 1.200 (1.020 ~ 1.411)]. (3) According to SNP rs2237895 genotype AA, AC, CC, the HOMA-B values of the subjects were (158.15 ± 99.66), (141.72 ± 132.62) and (131.54 ± 189.85) respectively, the difference was significant = 0.021), pregnant women with genotype CC had the smallest HOMA-B value. At the same time, the locus was also significantly different in the dominant model (P = 0.005) [HOMA-B (140.25 ± 142.15) (AC + CC) vs (158.15 ± 99.66) (AA)]. Conclusions There is a correlation between KCNQ1 SNP and GDM in Chinese population, which may be related to the more vulnerable pancreatic β-cell function in individuals with risk genes.