CAJ | 학술논문

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mtDNA ND2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x2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,mtDNA 5178A组的'T2DM患者收缩压为(124.6±9.0) mm Hg,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(=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(x2=8.832,P=0.003).C 5178A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) mm Hg和(128.0±9.0) mm Hg,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(x2 =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(x2=3.946,P=0.047;t=3.511,P=0.001).结论在T2DM患者中,mtDNA C5178A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. 目的探討線粒體DNA (mtDNA) ND2基因C5178A多態性與2型糖尿病(T2DM)患者併髮心腦血管病的關繫.方法本研究屬于病例對照研究.選擇2010至2011年期間在浙江省人民醫院住院的448例無血緣關繫的T2DM患者,男274例,女174例,採用PCR產物直接測序法對所有患者的mtDNA ND2基因5178位點進行測序,同時收集每例患者的臨床資料.根據測序結果分為5178C和5178A兩組,檢測所有患者的體重指數、血壓、血脂、血糖,通過t檢驗和x2檢驗,分析這些指標在T2DM患者5178C基因組和T2DM患者5178A基因組兩組之間的差異以及不同性彆的患者中的差異.結果在448例T2DM患者中共檢測齣348例5178C,100例5178A,mtDNA 5178A組的'T2DM患者收縮壓為(124.6±9.0) mm Hg,高密度脂蛋白(HDL)為(1.3±0.2)mmol/L,而5178C組的患者收縮壓為(127.8±10.7)mmHg、HDL為(1.2±0.3)mmol/L,兩組之間比較5178A組收縮壓降低,HDL升高(=2.700,P=0.007;t =2.968,P=0.003).5178A組腦梗死的髮生率為8.0％ (8/100),5178C組腦梗死的髮生率為21.0％(73/348),腦梗死的髮生率在兩組之間的差異有統計學意義(x2=8.832,P=0.003).C 5178A的變異在不同性彆之間的分佈沒有統計學差異(P＞0.05),進一步分析髮現在女性T2DM患者中,5178A和5178C組的三酰甘油水平分彆為(1.5±0.8)mmol/L和(1.8±1.0) mmol/L,收縮壓分彆為(123.6±6.6) mm Hg和(128.0±9.0) mm Hg,兩組之間比較5178A組女性患者三酰甘油和收縮壓明顯降低(t=2.601,P=0.011；t=2.887,P=0.004).女性5178A患者腦梗死的髮生率為5.3％(2/38),5178C女性患者腦梗死髮生率為21.3％(29/136),兩組之間的差異有統計學意義(x2 =5.232,P =0.022).在男性T2DM患者中,5178A組和5178C組的腦梗死髮生率分彆為9.7％(6/62)和20.7％ (44/212),HDL水平分彆為(1.4±0.2)mmol/L和(1.2±0.3) mmol/L,兩組比較5178A組男性患者腦梗死髮生率明顯降低,HDL水平明顯升高(x2=3.946,P=0.047;t=3.511,P=0.001).結論在T2DM患者中,mtDNA C5178A為多態性位點,該位點的改變與T2DM患者併髮心腦血管病存在相關性,其對血壓、血脂等的影響可能有利于牴抗T2DM患者心腦血管併髮癥的髮生髮展.
목적 탐토선립체DNA (mtDNA) ND2기인C5178A다태성여2형당뇨병(T2DM)환자병발심뇌혈관병적관계.방법 본연구속우병례대조연구.선택2010지2011년기간재절강성인민의원주원적448례무혈연관계적T2DM환자,남274례,녀174례,채용PCR산물직접측서법대소유환자적mtDNA ND2기인5178위점진행측서,동시수집매례환자적림상자료.근거측서결과분위5178C화5178A량조,검측소유환자적체중지수、혈압、혈지、혈당,통과t검험화x2검험,분석저사지표재T2DM환자5178C기인조화T2DM환자5178A기인조량조지간적차이이급불동성별적환자중적차이.결과 재448례T2DM환자중공검측출348례5178C,100례5178A,mtDNA 5178A조적'T2DM환자수축압위(124.6±9.0) mm Hg,고밀도지단백(HDL)위(1.3±0.2)mmol/L,이5178C조적환자수축압위(127.8±10.7)mmHg、HDL위(1.2±0.3)mmol/L,량조지간비교5178A조수축압강저,HDL승고(=2.700,P=0.007;t =2.968,P=0.003).5178A조뇌경사적발생솔위8.0％ (8/100),5178C조뇌경사적발생솔위21.0％(73/348),뇌경사적발생솔재량조지간적차이유통계학의의(x2=8.832,P=0.003).C 5178A적변이재불동성별지간적분포몰유통계학차이(P＞0.05),진일보분석발현재녀성T2DM환자중,5178A화5178C조적삼선감유수평분별위(1.5±0.8)mmol/L화(1.8±1.0) mmol/L,수축압분별위(123.6±6.6) mm Hg화(128.0±9.0) mm Hg,량조지간비교5178A조녀성환자삼선감유화수축압명현강저(t=2.601,P=0.011；t=2.887,P=0.004).녀성5178A환자뇌경사적발생솔위5.3％(2/38),5178C녀성환자뇌경사발생솔위21.3％(29/136),량조지간적차이유통계학의의(x2 =5.232,P =0.022).재남성T2DM환자중,5178A조화5178C조적뇌경사발생솔분별위9.7％(6/62)화20.7％ (44/212),HDL수평분별위(1.4±0.2)mmol/L화(1.2±0.3) mmol/L,량조비교5178A조남성환자뇌경사발생솔명현강저,HDL수평명현승고(x2=3.946,P=0.047;t=3.511,P=0.001).결론 재T2DM환자중,mtDNA C5178A위다태성위점,해위점적개변여T2DM환자병발심뇌혈관병존재상관성,기대혈압、혈지등적영향가능유리우저항T2DM환자심뇌혈관병발증적발생발전.
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 in ）patients.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 2analyzed whether these differences exist in patients with different gender by using t test or x2 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 ; x2 =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 128.0 mm Hg ± 9.0 mm Hg,respectively).Furthermore,cerebral infarction was more common in female T2DM patients with 5178C (21.3％,29/136; x2 =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; x2 =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.