Comprehensive genetic analysis of the dipeptidyl peptidase-4 gene and cardiovascular disease risk factors in obese individuals

被引：51

作者：

Bouchard, Luigi ^{[1
,2
,3
]}

Faucher, Genevieve ^{[1
,2
,3
]}

Tchernof, Andre ^{[2
,3
,4
]}

Deshaies, Yves ^{[5
,6
]}

Lebel, Stefane ^{[7
]}

Hould, Frederic-Simon ^{[7
]}

Marceau, Picard ^{[7
]}

Vohl, Marie-Claude ^{[1
,2
,3
]}

机构：

[1] Univ Laval, Lipid Res Ctr, Quebec City, PQ G1V 4G2, Canada

[2] Univ Laval, Nutraceut & Funct Foods Inst, Quebec City, PQ G1V 4G2, Canada

[3] Univ Laval, Dept Food Sci & Nutr, Quebec City, PQ G1V 4G2, Canada

[4] Univ Laval, Mol Endocrinol & Oncol Res Ctr, Quebec City, PQ G1V 4G2, Canada

[5] Univ Laval, Dept Anat & Physiol, Quebec City, PQ G1V 4G2, Canada

[6] Univ Laval, Laval Hosp, Quebec City, PQ G1V 4G2, Canada

[7] Univ Laval, Fac Med, Dept Surg, Quebec City, PQ G1V 4G2, Canada

来源：

ACTA DIABETOLOGICA | 2009年 / 46卷 / 01期

基金：

加拿大健康研究院;

关键词：

Metabolic syndrome; Diabetes; Candidate gene; Polymorphism; Association study; GLUCOSE-INTOLERANCE; ASSOCIATION; PREVALENCE; EXPRESSION; CATALYSIS; DESIGNS; IMPACT; QUEBEC; CD26;

D O I：

10.1007/s00592-008-0049-4

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

The incretin system has been shown to stimulate insulin secretion in a glucose dependent manner and currently fosters considerable hope for the treatment of diabetes. Recently, we have shown that the dipeptidylpeptidase-4 (DPP4) gene, which is responsible for incretin inactivation, was overexpressed in omental adipose tissue of obese men with the metabolic syndrome, compared to men not characterized by this condition. Since the cardiovascular disease (CVD) risk profile shows substantial inter-individual variability in obesity, this study aimed at verifying whether DPP4 polymorphisms contribute to explain such a difference. In the first step of this multi-stage study, seven tagging SNPs were genotyped in a sample of 576 obese (BMI > 40 kg/m(2)) individuals and tested for their association with blood pressure and lipids, as well as diabetes-related phenotypes. Then, in an additional sample of 572 obese individuals (stage 2), SNPs showing trends (P < 0.10) for an association in the first sample were genotyped and reanalyzed. Logistic regressions were used to compute odds ratio for obesity-related metabolic complications. In sample 1, homozygotes for rs17848915 and rs7608798 minor alleles were at lower risk of hyperglycemia/diabetes (P = 0.002) and elevated plasma triglyceride levels (P = 0.030) respectively, whereas rs1558957 heterozygotes were at higher risk to have high plasma triglyceride (P = 0.040), HDL- (P = 0.021), LDL- (P = 0.001) and total-cholesterol (P = 0.003) levels. However, none of these associations was consistently replicated in stage 2. This first comprehensive genetic analysis does not support the notion that DPP4 polymorphisms could modulate the CVD risk profile among obese patients.

引用

页码：13 / 21

页数：9

共 28 条

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N-linked glycosylation of dipeptidyl peptidase IV (CD26): Effects on enzyme activity, homodimer formation, and adenosine deaminase binding [J].