线粒体ND2基因C5178A多态性与2型糖尿病患者并发心脑血管病的关系评价

Assessment of mitochondrial DNA ND2 gene C5178A polymorphism for cerebral-cardiovascular complications in patients with type 2 diabetes mellitus

目的探讨线粒体DNA（mtDNA）ND2基因C5178A多态性与2型糖尿病（T2DM）患者并发心脑血管病的关系。方法本研究属于病例对照研究。选择2010至2011年期间在浙江省人民医院住院的448例无血缘关系的T2DM患者，男274例，女174例，采用PCR产物直接测序法对所有患者的mtDNAND2基因5178位点进行测序，同时收集每例患者的临床资料。根据测序结果分为5178C和5178A两组，检测所有患者的体重指数、血压、血脂、血糖，通过t检验和χ2检验，分析这些指标在T2DM患者5178C基因组和T2DM患者5178A基因组两组之间的差异以及不同性别的患者中的差异。结果在448例T2DM患者中共检测出348例5178C，100例5178A，mtDNA5178A组的T2DM患者收缩压为（124．6±9．0）mmHg，高密度脂蛋白（HDL）为（1．3±0．2）mmol／L，而5178C组的患者收缩压为（127．8±10．7）mmHg、HDL为（1．2±0．3）mmol／L，两组之间比较5178A组收缩压降低，HDL升高（t=2．700，P=0．007；t=2．968，P=0．003）。5178A组脑梗死的发生率为8．0％（8／100），5178C组脑梗死的发生率为21．0％（73／348），脑梗死的发生率在两组之间的差异有统计学意义（χ2=8．832，P=0．003）。C5178A的变异在不同性别之间的分布没有统计学差异（P〉0．05），进一步分析发现在女性T2DM患者中，5178A和5178C组的三酰甘油水平分别为（1．5±0．8）mmol／L和（1．8±1．0）mmol／L。收缩压分别为（123．6±6．6）mmHg和（128．0±9．0）mmHg，两组之间比较5178A组女性患者三酰甘油和收缩压明显降低（t=2．601，P=0．011；t=2．887，P=0．004）。女性5178A患者脑梗死的发生率为5．3％（2／38），5178C女性患者脑梗死发生率为21．3％（29／136），两组之间的差异有统计学意义（χ2=5．232，P=0．022）。在男性T2DM患者中，5178A组和5178C组的脑梗死发生率分别为9．7％（6／62）和20．7％（44／212），HDL水平分别为（1．4±0．2）mmol／L和（1．2±0．3）mmol／L，两组比较5178A组男性患者脑梗死发生率明显降低，HDL水平明显升高（χ2=3．946，P=0．047；t=3．511，P=0．001）。结论在T2DM患者中，mtDNAC5178A为多态性位点，该位点的改变与T2DM患者并发心脑血管病存在相关性，其对血压、血脂等的影响可能有利于抵抗T2DM患者心脑血管并发症的发生发展。

Objective To assess the relationship between mitochondrial DNA （mtDNA） ND2 gene C5178A polymorphism and complications of cardio-cerebral-vascular in patients with type 2 diabetes mellitus （T2DM）. Methods This is a case-control study. 448 unrelated patients with T2DM were collected from Zhejiang Provincial People＇s Hospital from 2010 to 2011, including 274 males and 174 females. Direct nucleotide sequencing analysis was used to screen mtDNA ND2 gene C5178A genotyping inpatients. Meanwhile, detailed clinical and laboratory information for all of study subjects were collected. Body mass index （BMI）, blood pressure, blood lipid, blood glucose and incidence rate of cerebral infarction were compared between 5178C patients and 5178A patients. Furthermore, according to the genotyping results, we 2 analyzed whether these differences exist in patients with different gender by using t test or χs test. Results 348 out of 448 patients with T2DM were C carriers and the remaining patients were A carriers. There＇re significant differences between T2DM patients with 5178A and T2DM patients with 5178C on systolic pressure （ 124. 6 mm Hg ±9.0 mm Hg vs 127.8 mm Hg ± 10. 7 mm Hg, t =2. 700,P =0. 007） and HDL （ 1.3 mmol/L ± 0. 2 mmol/L vs 1.2 mmol/L ± 0. 3 mmol/L, t = 2. 968, P = 0. 003 ）. Moreover, the incidence of cerebral infarction in T2DM patients with 5178A （ 8.0%, 8/100） was much lower than that with 5178C （21.0% , 73/348 ; χ2 = 8. 832, P = 0. 003）. No statistical gender difference was found in the distribution of C5178A （P 〉 0.05 ）. Our results also revealed that the female T2DM patients with 5178A had a lower serum triglyceride （ 1.5 mmol/L± 0. 8 mmol/L ; t = 2. 601, P = 0. 011 ） and lower systolic pressure （123.6 mm Hg±6.6 mm Hg; t =2.887, P =0.004） than that with 5178C （1.8 mmol/L ± 1.0 mmol/L and t28.0 mm Hg ± 9. 0 mm Hg, respectively）. Furthermore, cerebral infarction was more common in female T2DM patients with 5178C （21.3%, 29/136;χ2 = 5. 232, P = 0. 022） than that with 5178A （5.3% , 2/38）. Similarly, male T2DM patients with 5178A had a much lower incidence rate of cerebral infarction （9. 7%, 6/62; χ2 =3. 946, P =0. 047） than that with 5178C （20. 7%, 44/212）. In contrary, the serum concentration of HDL was higher in male T2DM patients with 5178A （ 1.4 mmol/L ±0. 2 mmol/L; t= 3.511, P = 0.001） than that with 5178C （1.2 mmol/L ± 0.3 mmol/L） .Conclusions The polymorphism site mtDNA C5178A correlates with cerebral-cardiovascular complications in patients with type 2 diabetes mellitus, mtDNA 5178A allele may protect T2DM patients from developing cerebral-cardiovascular diseases through regulation of blood pressure and lipid metabolism.