Elsevier

Atherosclerosis

Volume 150, Issue 1, May 2000, Pages 149-157
Atherosclerosis

Gender related association between genetic variations of APOC-III gene and lipid and lipoprotein variables in northern France

https://doi.org/10.1016/S0021-9150(99)00362-7Get rights and content

Abstract

The goal of the present study was to assess the impact of variability at the APOC-III insulin response element (APOC-III IRE) genetic locus on lipid, lipoprotein and complex lipoprotein particle levels as well as on the risk of dyslipidemia, in the population of northern France. To this end, 590 men and 579 women were randomly selected in the urban community of Lille in the framework of the MONICA project. Three polymorphisms, −482, −455 in the APOC-III insulin response element (IRE) and SstI in the 3′-noncoding region of the APOC-III gene locus were assessed. Compared to the most common alleles, the rare alleles of –482 and –455 were associated with increased levels of apoB-containing particles (LDL-cholesterol, apoB) and of triglyceride-related markers (apoC-III and LpC-III:B) in women, but not in men, suggesting a gender-related impact of APOC-III polymorphisms on these variables. Similarly, triglycerides, LpC-III:B and apoB were higher in women bearing the rare allele of SstI than in those with the most common allele. There was no evidence for any significant association between any of the −482, −455, and SstI alleles and lipid disorders (mixed hyperlipidemia, hypertriglyceridemia and hypercholesterolemia) in this sample of randomly selected men and women from northern France. In contrast, the prevalence of the haplotype that combined the rare alleles of the −482 and −455 sites was increased only in women with hypertriglyceridemia. Therefore, although the individual risk of hypertriglyceridemia is increased in women with the haplotype T, C at −482, −455, it appears that the −482, −455 and SstI APOC-III gene polymorphisms are not major contributors to the risk of dyslipidemia in the population of northern France.

Introduction

ApoC-III is synthesized mainly in the liver and is a constituent of very-low-density lipoprotein (VLDL) and HDL [1]. Because apoC-III is involved in the transport and metabolism of cholesterol, it is a candidate for determining genetic associations with serum lipid or lipoprotein levels and dyslipidemia [2]. Several cohort studies [3], [4], [5], [6], [7], [8], [9], [10], [11], as well as case-control [12], [13], [14], [15], [16], [17], [18] and familial [19], [20], [21], [22], [23] studies support the concept that polymorphic sites at the genetic locus of APOC-III are associated with particular lipid and lipoprotein phenotypes suggesting that APOC-III gene variability contributes to the risk of lipid disorders. However, these results were not confirmed in other reports [22], [23], [24], [25], [26], [27]. The possible reasons for these discrepancies include population-specific associations, environmental influences or methodological flaws such as biased or small-sized samples or nonrandomized selection of subjects.

In a previous work, we found no association between variability at the SstI APOC-III gene site (in the 3′-noncoding region) and lipid, lipoproteins and complex lipoprotein particles in a sample of men from northern France [28]. The later study left two questions open for investigation. The first was whether the association between SstI APOC-III gene polymorphism and serum lipoprotein or lipoprotein particles is gender-related, and the second was whether other polymorphisms in the APOC-III gene are associated with lipoprotein variability. The goal of the present study was to answer these questions. To this end, the relationships between lipid, lipoprotein or lipoprotein particle levels and SstI site or two polymorphisms in the APOC-III IRE (−455, −482) were analyzed in men and women randomly sampled from the urban community of Lille.

Section snippets

Subjects

The population sample was composed of 1195 men and women, living in the urban community of Lille (northern France), aged between 35 and 65 years, who were randomly selected from the electoral rolls, and stratified on gender and 10-year age groups. This sample was recruited within the framework of the WHO-MONICA (World Health Organization-MONItoring of trends and determinants of CArdiovascular disease) project. A questionnaire was completed, which included details on personal medical history,

Subjects characteristics

The mean age and BMI were similar in both genders. The waist circumference, waist to hip ratio, systolic and diastolic blood pressure were greater in men than in women (Table 1). There were significantly more smokers (P<0.0001) and more subjects with a personal history of dyslipidemia (P<0.04) or coronary heart disease (P<0.0001) in men than in women. Conversely there was no statistically significant difference in the prevalence of hypertension or diabetes mellitus between gender. As expected,

Discussion

The major finding of the present study was that genetic variability at −482, −455 and SstI APOC-III gene sites is associated with variability in triglyceride-rich and apolipoprotein B containing lipoproteins in women but not in men indicating a gender-dependent relationship. Despite these associations, APOC-III gene variability had no significant impact on the prevalence of dyslipidemia in men and women. In contrast, the haplotype combining the rare alleles of −482 and −455 sites was associated

Acknowledgements

The authors wish to thank Mrs. V. Codron, Mr. X. Hermant and Mr. Eric Baugé for technical assistance. Mrs. A. Meirhaeghe was supported by a grant from the Ministère de l’Enseignement Supérieur et de la Recherche. The WHO-MONICA population study developed in the north of France was supported by unrestricted grants from the Conseil Régional du Nord-Pas de Calais, ONIVINS, Parke-Davies Laboratory, the Mutuelle Générale de l’Education Nationale (MGEN), Groupe Fournier, the Réseau National de Santé

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