脂蛋白脂肪酶 HindIII 和 PvuII 基因多态性与 2 型糖尿病患者脂质代谢及大血管事件的关联

. Association of HindIII and PvuII genetic polymorphisms of lipoprotein lipase with lipid metabolism and macrovascular events in type 2 diabetic patients.

作者信息

Socquard E, Durlach A, Clavel C, Nazeyrollas P, Durlach V

机构信息

Service d'Endocrinologie, Maladies Métaboliques et de Médecine Interne, Hôpital Robert Debré, Centre Hospitalo-Universitaire, 51092 Reims, France.

出版信息

Diabetes Metab. 2006 Jun;32(3):262-9. doi: 10.1016/s1262-3636(07)70278-1.

DOI:10.1016/s1262-3636(07)70278-1

PMID:16799404

Abstract

AIM

Lipoprotein lipase (LPL) is a key enzyme of lipid metabolism, and its genetic polymorphism may be a candidate for modulating lipid parameters in type 2 diabetic subjects (D2).

METHODS

In a group of 404 type 2 diabetic patients, aged 59.5+/-10.8y, BMI=28.9+/-5.3 kg/m2, HbA1c=8.2+/-1.9%, we studied the H and P polymorphisms at the LPL locus detectable with the restriction enzymes HindIII and PvuII. Patients were separated into 229 males (17H1H1, 84H1H2, 128H2H2 and 51P1P1, 110P1P2, 68P2P2) and 175 females (16H1H1, 69H1H2, 90H2H2 and 51P1P1, 85P1P2, 39P2P2), and compared on the basis of their lipid parameters and their macrovascular complications.

RESULTS

Triglyceride (TG) and HDL-cholesterol(c) concentrations differed between patients with and without coronary heart disease (CHD) (3.44+/-2.09 and 1.96+/-1.40 mmol/l for TGs and 1.05+/-0.24 and 1.34+/-0.40 mmol/l for HDL-c, P<0.001). HDL-c concentrations were lower in male H2H2 and P2P2 subjects (P<0.001), and TG levels were higher in male H2H2 and P2P2 subjects (P<0.0001 for Hind III and P<0.05 for PvuII). Allele frequency of the HindIII and PvuII restriction site was similar to those reported in other Caucasian populations and the presence of the H2/P2 variants was significantly higher in CHD patients. The prevalence of CHD in this population was 18% but was 29% in H2H2 and 38% in P2P2 subjects (P<0.02).

CONCLUSION

Thus, HindIII and PvuII polymorphisms seem to exert a modulating role on lipid profile particularly in male D2, contributing to increase the risk of macrovascular events.

摘要

目的

脂蛋白脂肪酶（LPL）是脂质代谢的关键酶，其基因多态性可能是调节2型糖尿病患者（D2）脂质参数的一个候选因素。

方法

在一组404例2型糖尿病患者中，年龄59.5±10.8岁，体重指数（BMI）=28.9±5.3kg/m2，糖化血红蛋白（HbA1c）=8.2±1.9%，我们研究了用限制性内切酶HindIII和PvuII可检测到的LPL基因座的H和P多态性。患者分为229名男性（17例H1H1、84例H1H2、128例H2H2和51例P1P1、110例P1P2、68例P2P2）和175名女性（16例H1H1、69例H1H2、90例H2H2和51例P1P1、85例P1P2、39例P2P2），并根据其脂质参数和大血管并发症进行比较。

结果

有冠心病（CHD）和无冠心病的患者之间甘油三酯（TG）和高密度脂蛋白胆固醇（HDL-c）浓度存在差异（TG分别为3.44±2.09和1.96±1.40mmol/l，HDL-c分别为1.05±0.24和1.34±0.40mmol/l，P<0.001）。男性H2H2和P2P2受试者的HDL-c浓度较低（P<0.001），男性H2H2和P2P2受试者的TG水平较高（HindIII酶切为P<0.0001，PvuII酶切为P<0.05）。HindIII和PvuII限制性位点的等位基因频率与其他白种人群报道的相似，且CHD患者中H2/P2变异体的存在显著更高。该人群中CHD的患病率为18%，但H2H2受试者中为29%，P2P2受试者中为38%（P<0.02）。