生殖医学杂志

目的 分析脂联素、瘦素及其受体基因多态性与妊娠期糖尿病(GDM)患病的可能关系。方法 本研究为病例-对照研究设计。根据孕24～28周口服葡萄糖耐量试验(OGTT)结果，收集2019年1—12月在我院常规产检的156例葡萄糖耐量正常(NGT)孕妇为对照组，162例GDM孕妇为病例组。使用单碱基末端延伸(SNaPshot)PCR方法对两组研究对象脂联素ADIPOQ1基因单核苷酸多态性(SNP)位点rs266729、rs17300539,ADIPOQ2基因SNP位点rs1501299、rs2241766,脂联素受体ADIPOQR1基因SNP位点rs1539355,瘦素OGDH基因SNP位点rs12112075和瘦素受体LEPR基因SNP位点rs1137101进行分型分析。结果 脂联素ADIPOQ1基因rs266729位点的GG基因型、等位基因G在病例组的分布频率较对照组显著降低(P<0.001);脂联素ADIPOQ2基因rs1501299位点的TT基因型、等位基因T在病例组的分布频率较对照组显著升高(P<0.001),rs2241766位点的GG基因型、等位基因G在病例组的分布频率亦较对照组显著升高(P<0.001);瘦素OGDH基因及瘦素受体LEPR基因位点基因型分布及频率在两组间无统计学差异(P>0.05)。多因素分析显示脂联素基因rs266729与rs2241766位点突变可致GDM患病风险增加，其OR(95%CI)分别为4.09(2.08,8.06)和2.77(1.63,4.74)(P<0.001)。基因交互作用分析结果显示，脂联素ADIPOQ1基因SNP位点rs266729和ADIPOQ2基因SNP位点rs2241766的分布之间存在交互作用，二者的联合作用导致GDM患病风险增加[OR(95%CI)为4.83(1.57,11.42),P<0.001]。结论 脂联素ADIPOQ1基因SNP位点rs266729和ADIPOQ2基因SNP位点rs2241766的基因突变增加GDM的患病风险；二者联合作用与GDM的发生有关。瘦素及瘦素受体位点基因型分布及频率与GDM的发生无明显关系。

Objective:To analyze the association between gene polymorphisms of adiponectin, leptin and their receptors and gestational diabetes mellitus(GDM).Methods:This case-control study included 162 pregnant women with GDM(GDM group) and 156 pregnant women with normal glucose tolerance(NGT)(control group) based on the oral glucose tolerance test(OGTT) at 24-28 weeks' gestation in our hospital from Jan. to Dec. 2019. The typing of single nucleotide polymorphism(SNP) sites of adiponectin ADIPOQ1 rs266729 & rs17300539,ADIPOQ2 gene SNP sites rs1501299 & rs2241766,adiponectin receptor ADIPOQR1 gene SNP sites rs1539355,leptin OGDH gene SNP site rs12112075 and leptin receptor LEPR gene SNP site rs1137101 were analyzed by using single base end extension(SNaPshot) PCR method.Results:The distribution frequency of GG genotype and allele G at rs266729 locus of adiponectin ADIPOQ1 gene in the GDM group was significantly lower than that in the control group(P<0.001). The distribution frequency of TT genotype and allele T at rs1501299 of adiponectin ADIPOQ2 gene in the GDM group was significantly higher than that in the control group(P<0.001). The distribution frequency of GG genotype and allele G at the rs2241766 locus of adiponectin ADIPOQ2 gene in the GDM group was significantly higher than that in the control group(P<0.001). There was no significant difference in genotype distribution and frequency of the loci of leptin OGDH gene and leptin receptor LEPR gene between the two groups(P>0.05). Multivariate analysis showed that mutations at rs266729 and rs2241766 of adiponectin gene increased the risk of GDM[OR(95%CI)=4.09(2.08,8.06) and 2.77(1.63,4.74),respectively](P<0.001). The results of gene interaction analysis showed that there was interaction between the distribution of SNP site rs266729 of adiponectin ADIPOQ1 gene and SNP site rs2241766 of ADIPOQ2 gene. The combination of the two effects led to an increased risk of GDM[OR(95%CI)=4.83(1.57,11.42),P<0.001].Conclusions:Mutations in the SNP locus rs266729 of adiponectin ADIPOQ1 gene and rs2241766 of ADIPOQ2 gene increase the risk of GDM. The interaction of the two SNPs is associated with GDM. The genotype distribution and frequency of loci of leptin and leptin receptor are not significantly related to the occurrence of GDM.