云南地区汉族2型糖尿病患者二甲基精氨酸二甲胺水解酶1、二甲基精氨酸二甲胺水解酶2基因单核苷酸多态性与动脉粥样硬化关系的研究

The relationship between single nucleotide polymorphisms of DDAH1 and DDAH2 gene and atherosclerosis in type 2 diabetic patients of Han nationality in Yunnan

目的探讨云南地区汉族T2DM患者发生动脉粥样硬化(AS)与二甲基精氨酸二甲胺水解酶1(DDAH1)基因rs233113、二甲基精氨酸二甲胺水解酶2(DDAH2)基因rs805304单核苷酸多态性(SNP)的相关性。方法选取2016年10月至2018年12月于昆明医科大学第一附属医院内分泌二科住院的T2DM患者464例,根据有无AS分为单纯T2DM组(n=208)和合并AS组(AS,n=256)。另选取同期我院体检健康人群294名为正常对照(NC)组。ELISA法检测各组血浆非对称性二甲基精氨酸(ADMA)的浓度,聚合酶链反应‐限制性片段长度多态性分析法(PCR‐RFLP)对DDAH1、DDAH2基因SNP进行基因分型。结果T2DM、AS组CC基因型频率高于NC组(P<0.05),AS组CC基因型频率高于T2DM组(P<0.05)。AS组DDAH1基因rs233113 AA基因型ADMA水平低于TT+AT基因型(P<0.05),DDAH2基因rs805304 CC基因型LDL‐C水平高于AA、AC基因型(P<0.05)。Logistic回归分析显示,SBP、FPG、LDL‐C、ADMA、DDAH2基因rs805304位点CC基因型是T2DM患者发生AS的影响因素。结论云南地区汉族T2DM患者DDAH2基因rs805304 CC基因型可能与AS易感性相关,携带该基因型患者LDL‐C水平升高。DDAH1基因rs233113位点SNP可能与T2DM发生AS无相关性,携带该位点AA基因型患者ADMA水平降低。

Objective To investigate the relationship between the single nucleotide polymorphism(SNP)rs233113 and rs805304 in DDAH1 and DDAH2 gene and T2DM with atherosclerosis(AS)in Han nationality in Yunnan province.Methods A total of 464 T2DM patients were selected from the First Affiliated Hospital of Kunming Medical University from October 2016 to December 2018.The subjects were divided into T2DM group(n=208)and AS group(AS,n=256).In addition,294 healthy people who underwent physical examination during the same period were selected as the normal control(NC)group.Plasma asymmetric dimethylarginine(ADMA)concentration was detected by ELISA.SNPs in DDAH1 and DDAH2 were genotyped by PCR‐RELP.Results Compared with NC group,CC genotype frequency increased in T2DM and AS group(P<0.05).The CC genotype frequency in AS group was higher than that in T2DM group(P<0.05).The ADMA level in patients with DDAH1 gene rs233113 AA genotype in AS group was lower than that of TT and AT genotype(P<0.05).The LDL‐C level in patients with DDAH2 gene rs805304 CC genotype was higher than that of AA and AC genes(P<0.05).Logistic regression showed that SBP,FPG,LDL‐C,ADMA and DDAH2 gene rs805304 CC genotype may be the risk factors of AS in T2DM patients.Conclusion DDAH2 gene rs805304CC genotype may be related to AS in Han T2DM patients in Yunnan,China.The levels of LDL‐C in patients carrying rs805304 CC genotype are increased.The SNP rs233113 in DDAH1 gene may have no correlation with AS in T2DM patients,but having lower ADMA levels in those with rs233113AA genotype.