PXR基因单核苷酸多态性与2型糖尿病患病风险的关系

Relationship between single nucleotide polymorphism of PXR gene and risk of type 2 diabetes mellitus

目的探讨孕烷X受体(PXR)基因单核苷酸多态性(SNP)与2型糖尿病(T2DM)患病风险的关系。方法选择T2DM患者285例(观察组)、同期体检健康的志愿者230例(对照组),采集所有研究对象空腹外周静脉血,提取基因组DNA,然后对PXR基因rs1523127、rs3814055、rs6785049位点进行测序和基因分型;采用ELISA法检测血清PXR、葡萄糖转运体2(GLUT2)、葡萄糖激酶(GCK)。比较两组PXR基因rs1523127、rs3814055、rs6785049位点基因型及等位基因频率,以及血清PXR、GLUT2、GCK水平。分析PXR基因SNP与T2DM患病风险的关系。结果经Hardy-Weinberg遗传平衡检验,两组PXR基因不同位点基因型、等位基因频率均符合遗传平衡定律。两组PXR基因rs1523127、rs6785049位点基因型及等位基因频率比较差异均无统计学意义(P均>0.05)。观察组PXR基因rs3814055位点CT/TT基因型及T等位基因频率均高于对照组(P均<0.05),携带CT、TT基因型者罹患T2DM的优势比(OR)分别为携带CC基因型者的1.591、2.398倍,携带T等位基因者罹患T2DM的OR为携带C等位基因者的1.638倍。观察组血清PXR水平高于对照组,血清GLUT2、GCK水平低于对照组(P均<0.05)。T2DM患者PXR基因rs3814055位点CT/TT基因型者血清PXR水平高于CC基因型者,血清GLUT2、GCK水平低于CC基因型者(P均<0.05)。结论PXR基因rs3814055位点C等位基因突变为T等位基因能够增加其转录活性,抑制血清GLUT2、GCK水平,使其糖耐量受损,进而增加T2DM的患病风险。

Objective To investigate the relationship between the single nucleotide polymorphism(SNP)of preg‑nane X receptor(PXR)gene and the risk of type 2 diabetes mellitus(T2DM).Methods Totally 285 T2DM patients(observation group)and 230 healthy volunteers(control group)were selected.Fasting peripheral venous blood of all sub‑jects was collected,genomic DNA was extracted,and PXR gene sites rs1523127,rs3814055 and rs6785049 were sequenced and genotyping was performed.Serum PXR,glucose transporter 2(GLUT2)and glucokinase(GCK)were detected by enzyme ELISA.The genotypes and allele frequencies of rs1523127,rs3814055,rs6785049 and serum levels of PXR,GLUT2 and GCK were compared between the two groups.We analyze the relationship between SNP of PXR gene and the risk of T2DM.Results Through Hardy-Weinberg genetic balance test,the genotypes and allele frequencies of PXR genes at different loci were consistent with the law of genetic balance in the two groups.There were no significant dif‑ferences in genotypes or allele frequencies of rs1523127 and rs6785049 of PXR gene between two groups(all P>0.05).The frequencies of CT/TT genotype and T allele at rs3814055 of PXR gene in the observation group were higher than those in the control group(both P<0.05),and the odds ratio(OR)of T2DM patients with CT and TT genotype was 1.591 and 2.398 times higher than that of patients with CC genotype.The OR of T allele carriers for T2DM was 1.638 times higher than that of C allele carriers.Serum PXR level in the observation group was higher than that in the control group,and serum GLUT2 and GCK levels were lower than those in the control group(both P<0.05).The level of serum PXR in CT/TT genotype at rs3814055 of PXR gene in T2DM patients was higher than that in patients with CC genotype,and the levels of serum GLUT2 and GCK were lower than those in patients with CC genotype(both P<0.05).Conclusion The mutation of C allele at rs3814055 of PXR gene to T allele can increase its transcriptional activity,inhibit serum GLUT2 and GCK levels,impair glucose tolerance,and increase the risk of T2DM.