TCF7L2、CDKAL1、SLC30A8和HHEX基因多态性与2型糖尿病微血管并发症的相关性

Association analysis of genetic polymorphisms of TCFTL2, CDKALI, SLC3OA8, HHEX genes and microvascular complications of type 2 diabetes mellitus

目的研究TCF7L2、CDKAL1、SLC30A8和HHEX基因单核苷酸多态性（sing1enuc1eotidepo1ymorphism，SNP）与2型糖尿病微血管并发症的相关性。方法采用病例-对照方法分析研究对象[糖尿病视网膜病变组（diabeticretinopathy，DR）479例，糖尿病肾病组（diabeticnephropathy，DN）248例，对照组650名]的TCF7L2基因rs7903146、rs6585205、rs11196218位点，CDKAL1基因rs10946398、rs4712527位点，SLC30A8基因rs13266634、rs3802177、rs11558471位点，HHEX基因rs1111875、rs7923837位点多态性与DR、DN发病风险的关系。结果SLC30A8rs11558471的等位基因及基因型频率在DR与对照组间差异有统计学意义（P〈0．05），等位基因A、基因型AA的0R值分别为1．27、1．68，TCF7L2rs11196218的A等位基因在DN与对照组之间差异有统计学意义（P=0．0051，OR=1．37），但对P值做Bonferroni校正后差异无统计学意义。SLC30A8rs13266634和rs3802177，CDKAL1rs10946398，TCF7L2rs6585205、rs7903146、rs11196218，HHEXrs7923837的等位基因及基因型频率在DR组与对照组间比较差异无统计学意义（P〉0．05），TCF7L2rs6585205，CDKAL1rs4712527，SLC30A8rs13266634、rs3802177和rs11558471和HHEXrs7923837的等位基因和基因型频率在DN与对照组间差异无统计学意义，但是其相应的0R值都大于1。结论SLC30A8基因多态性可能与DR发病相关；TCF7L2基因多态性可能与DN发病相关；不能排除CDKAL1、TCF7L2、HHEx基因多态性与DR的相关性及SLC30A8、CDKAu、HHEX基因多态性与DN的相关性。

Objective To study the associations of single nucleotide polymorphisms （SNPs） of TCF7L2, CDKAL1, SLC3OAS, HHEX with diabetic retinopathy （DR） and nephropathy （DN） in type 2 diabetes mellitus. Methods A total of 479 subjects with DR,248 with DN and 650 without DR or DN were recruited to assess the associations between SNPs of TCF7L2 （rs7903146, rs6585205, rs11196218）, CDKAL1 （rs10946398, rs4712527）, SLC3OA8 （rs13266634, rs3802177, rs11558471） and HHEX （rs1111875,rs7923837） and the development of DR and DN. Results There were significant differences in genotypic and allele frequencies of rs11558471 （SLC3OA8）between DR and control groups （P〈0. 05）, the odds ratio （OR） values of A and AA were 1.27 and 1.68. The distributions of genotype and allele frequency for rs11196218 （TCF7L2）were significantly different between DN and control group （P = 0. 0051, OR= 1.37）. However, the P value after Bonferroni correction showed no significant difference. No significant differences were found in the distributions of rs13266634 and rs3802177 （SLC3OAS）, rs10946398 （CDKAL1） , rs6585205, rs7903146 and rs11196218 （TCF7L2） and rs7923837 （HHEX） between DR and control groups, and nor significant differences were found in distributions of rs6585205 （TCF7L2）, rs4712527 （CDKAL1）, rs13266634, rs3802177 and rs11558471 （SLC3OA8）, and 7923837 （HHEX） between DN and control groups, though for all comparison the OR values were greater than 1. Conclusion Polymorphisms of SLC3OA8 and TCF7L2 genes may be associated with the development of DR and DN, respectively. Association between the polymorphisms of CKDAL1, TCF7L2 and HHEX genes and DR, and between the polymorphisms of SLC3OA8 , HHEX and CDKAL1 genes and DN, cannot be excluded.