甲基供体代谢酶基因多态性与糖尿病并发症的关联性研究  

Association between genetic polymorphisms of serum methyl groups and diabetic complications

作　　者：魏俊[1] 王丽君[1] 王佳佳[1] 王娴[1] 钟淑婷[2] 常颖[1] 朱惠莲[1] 

机构地区：[1]中山大学公共卫生学院,广东广州510080 [2]广州医学院第三附属医院

出　　处：《华南预防医学》2012年第2期1-5,11,共6页South China Journal of Preventive Medicine

基　　金：国家自然科学基金(基金编号:30872099和81072302)

摘　　要：目的探讨甲基供体代谢酶亚甲基四氢叶酸还原酶(MTHFR)、甜菜碱-同型半胱氨酸甲基转移酶(BHMT)及磷脂酰乙醇胺-N-甲基转移酶(PEMT)基因多态性与糖尿病肾病和糖尿病视网膜病变的关联。方法选取2010年1月至10月在中山大学附属第三医院内分泌科接受治疗的2型糖尿病患者184例,按并发症情况分为单纯糖尿病组、糖尿病合并视网膜病变组、糖尿病合并肾病组。通过调查问卷获取研究对象的一般特征资料,检测血清血糖、血脂等生化指标。采用聚合酶链反应-限制性片段长度多态性技术分析基因多态性;高效液相色谱质谱联用法测定血清甲基供体甜菜碱和胆碱浓度;高效液相色谱法测定血清同型半胱氨酸水平。定量资料的比较采用t检验或单因素方差分析,分类变量比较采用2检验。糖尿病并发症危险因素分析采用非条件logistic回归分析。结果单纯糖尿病患者64例(男性27例,女性37例,平均年龄58.3岁),糖尿病合并视网膜病变患者61例(男性24例,女性37例,平均年龄59.3岁),糖尿病合并肾病患者59例(男性33例,女性26例,平均年龄60.4岁)。3组患者在性别、年龄方面差异无统计学意义(P>0.05)。糖尿病视网膜病变组PEMT G-774C的C等位基因频率(32.0%)低于单纯糖尿病组(50.0%)(P<0.01)。PEMT G-774C基因GG型血清胆碱平均水平(中位数,24.6μmol/L)低于GC+CC型(33.1μmol/L)(P<0.05);GG型血清同型半胱氨酸均值(17.0μmol/L)高于GC+CC型(13.8μmol/L)(P<0.01)。糖尿病视网膜病变组和糖尿病肾病组血清胆碱、甜菜碱平均水平(中位数)分别为8.23、25.5和10.5、24.8μmol/L,均低于单纯糖尿病组(25.0、30.8μmol/L)(P<0.05),血清同型半胱氨酸均值(18.4、19.0μmol/L)高于单纯糖尿病组(12.6μmol/L)(P<0.05);多因素logistic回归分析显示甜菜碱为视网膜病变及糖尿病肾病的保护因素(β值分别为-1.626和-1.743),同型半胱氨酸为危险因素(β值分别为5.321和Objective To investigate the association between MTHFR C677T, BHMT G742A, PEMT G-774C genetic polymorphisms in methyl group metabolism and diabetic complications. Methods 184 treated diabetics were selected from the third affiliated hospital of Sun Yat-sen University from Jan to Oct 2010 and divided into ncphropathy （DN group）, retinopathy （DR group） and single dia- betic patients （DM group）. The characteristics of the subjects were obtained by self-administrated ques- tionnaire. PCR-RFLP was used to identify the genetic polymorphisms of MTHFR C677T, BHMT G742A, and PEMT G-774C. The concentration of tHcy was determined by HPLC. The serum betaine and choline were detected by LC-MS/MS. Results There were 64 cases in DM group （27males and 37 females with the average age of 58.3 years old）, 61 cases in DR group （24 males, 37 females, average age 59.3）, 59 cases in DN group （33 males, 26 females, average age 60.4）. There were no statistically significant differences among the groups（P 〉0.05）. The callele frequency of PEMT G-774C was lower in DR group compared with DM group（32.0% vs 50.0% ,P 〈0.01 ）. The DN group and DR group had higher serum tHcy concentration but lower serum betaine and choline concentrations than DM group （ P 〈 0.05 ）, while the GG genotype had higher serum tHcy and lower choline level than GC ＋ CC genotype （P 〈 0.05 ）. Serum betaine might be the beneficial factor of diabetic retinopathy and diabetic nephropathy （/3： - 1. 626 and - 1. 743, respectively）, while serum homocysteine, the risk factor （β： 5. 321 and 2.007, respectively）, by logistic analysis. Conclusion PEMT G-774C GG genotype reduces the serum choline and increases the tHcy. Serum betaine was the favorable factor for diabetic retinopathy and diabetic nephropathy, while tH-cy, the risk factor.

关 键 词：甲基供体 磷脂酰乙醇胺-N-甲基转移酶 甜菜碱 糖尿病 

分 类 号：R587.1[医药卫生—内分泌]