Association of rs662799 variant and APOA5 gene haplotypes with metabolic syndrome and its components: a meta-analysis in North Africa.

Meriem Hechmi,Meriem Gharbi,Sonia Bahri,Hamza Dallali,Haifa Jmel,Yossra Ben Halima,Abdelhamid Barakat,Henda Jamoussi,Rym Kefi,Afaf Bahlous,Meriem Fassatoui,Abdelmajid Abid

doi:10.1042/bsr20200706

Abstract

Apolipoprotein A5 (APOA5) has been linked to metabolic syndrome (MetS) in several populations. In North Africa, only the Tunisian and Moroccan populations were investigated. Our aim is to assess the association between APOA5 gene variant (rs662799) and haplotypes with MetS in Tunisian population and to perform a meta-analysis in North Africa. A total of 594 Tunisian participants were genotyped for polymorphism rs662799 using KASPar technology. Two polymorphisms rs3135506 and rs651821 in APOA5 gene genotyped in our previous study, were used in addition to rs662799 to assess the haplotype association with MetS. The genotype of 875 participants was used for the meta-analysis. Statistical analyses were performed with R software.The rs662799 increases the risk of MetS under the dominant (P=0.018) and the additive models (P=0.028) in the Tunisian population. After stratification of the cohort following the sex and the geographic origin, a positive association of rs662799 with MetS was found for participant from the Northern region and for the women group. Only the haplotype AGT showed a significant association with MetS by decreasing the risk of the disease.The meta-analysis reported a significant association of rs662799 and rs3135506 with MetS.Our results showed a significant association between the APOA5 gene variants rs662799 and haplotypes with MetS and its traits in Tunisia. An impact of the sex and the geographic origin on the genotype distribution was highlighted. Our funding emphasizes the role of APOA5 in the development of MetS in North Africa.

Highlights

Metabolic syndrome (MetS) consists of a constellation of several metabolic abnormalities, including hypertension, dyslipidemia, abdominal obesity and insulin-resistance [1,2]
Our results showed significant differences of several features; high Waist Circumference (WC), Body mass index (BMI), impaired fasting plasma glucose (IFG), TG, diastolic blood pressure (DBP), systolic blood pressure (SBP), low-density lipoprotein (LDL) and low level of high-density lipoprotein (HDL) in MetS patients compared with controls (P
We studied the linkage disequilibrium (LD) between the Apolipoprotein A5 (APOA5) variants rs651821 and rs3135506 analyzed in our previous study [19] and the APOA5 variant rs662799 analyzed in the present study. r2 index was estimated for all pairs of polymorphisms

Summary

Introduction

Metabolic syndrome (MetS) consists of a constellation of several metabolic abnormalities, including hypertension, dyslipidemia, abdominal obesity and insulin-resistance [1,2]. The prevalence of MetS is 25% in the world [3] and 30% in Tunisia [4]. This chronic disease can evolve to serious complications such as type 2 diabetes and cardiovascular diseases increasing the morbidity and the mortality of MetS patients [5]. Two main factors are the origin of MetS; the genetic background and the environmental factors. An unhealthy diet and sedentary lifestyle lead to the development of MetS added to the genetic susceptibility [6,7]. Studies have identified several SNPs to be correlated with MetS and its complications through genome-wide association studies (GWASs) and candidate gene association studies. There is some inconsistency in the results of different studies

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