CBR3 rs1048303位点基因多态性与2型糖尿病相关性及其对瑞格列奈疗效的影响

Associations of CBR3 rs10483032 polymorphisms with type 2 diabetes mellitus and its effects on repaglinide therapeutic efficacy

目的:分析CBR3 rs10483032基因多态性在中国淮海地区汉族2型糖尿病(T2DM)患者与正常人群中的分布特征,并探讨该遗传多态性与T2DM易感性的关联及其对瑞格列奈疗效的影响。方法:采用三维聚丙烯酰胺凝胶DNA芯片对180名T2DM患者和101名健康对照者进行CBR3 rs10483032基因型分析;81名初诊初治的T2DM患者口服瑞格列奈1 mg,tid,持续8周;服药前和服药第8周末收集静脉血标本,测定糖脂代谢相关指标。应用非参数检验、两样本t检验、配对t检验和χ~2检验进行统计学分析。结果:CBR3 rs10483032位点G等位基因频率在T2DM组和健康对照组间分别为17.50%和8.91%,差异具有显著性(P<0.01)。在中国淮海地区汉族T2DM患者中,CBR3 rs10483032位点AG/GG基因型患者的空腹血清胰岛素(FINS)、餐后血清胰岛素(PINS)、稳态模型胰岛素抵抗指数(HOMA-IR)显著高于AA基因型患者,差异有显著性(P<0.05)。瑞格列奈连续治疗8周后,2组基因型之间各临床指标无明显差异(P>0.05)。结论:CBR3 rs10483032位点基因型和等位基因频率在T2DM患者及健康人群中分布存在明显差异,与中国淮海地区汉族人群T2DM发生相关;CBR3 rs10483032位点G等位基因携带者可能通过影响FINS、PINS、HOMA-IR值增加患T2DM风险。瑞格列奈治疗后,CBR3 rs10483032位点多态性与瑞格列奈疗效无关。

OBJECTIVE To analyze the distribution of CBR3 rs10483032 genetic polymorphism in type 2 diabetes mellitus（T2DM） patients and healthy subjects among the Han ethnic group in Huaihai region,and to investigate the associations between the genetic polymorphism and the susceptibility of T2DM as well as its effects on repaglinide response in T2DM patients. METHODS Totally 180 patients with T2DM and 101 healthy subjects were included to determine their genotypes for CBR3 rs10483032 polymorphism by three-dimensional polyacrylamide gel-based DNA microarray. Eighty one newly diagnosed T2DM patients were orally administrated 1 mg repaglinide three times per day for 8 consecutive weeks. Blood was collected to measure glucose and lipid metabolism related indicators before and after treatment. Statistical analyses were performed by the Wilcoxon rank sum test,the two-sample t test,the paired student＇s t test and Pearson＇s chi-square test. RESULTS The G allelic frequency of CBR3 rs10483032 in patients with T2DM and health controls were 17. 50% and 8. 91%,respectively（ P〈0.01）. The levels of FINS,PINS,and HOMA-IR in T2DM patients with AG/GG genotype of CBR3 rs10483032 were higher in comparison with those of AA genotype（ P〈0.05）. There was no significant difference in the clinical indexes between the AA and AG/GG genotypes after 8 weeks of continuous treatment with repaglinide（ P〉0.05）. CONCLUSION CBR3 rs10483032 genetic polymorphism may have effects on T2DM. There is significant difference in allelic frequency of CBR3 rs10483032 between T2DM patients and control subjects. T2DM patients with CBR3 rs10483032 G allele show higher in FINS,PINS,and HOMA-IR in comparison with those with A allele. CBR3 rs10483032 polymorphism is not associated with the efficacy of repaglinide.