Association between variants of the leptin receptor gene (LEPR) and overweight: a systematic review and an analysis of the CoLaus study.

Détails

Ressource 1Télécharger: BIB_739E357D2F3D.P001.pdf (1082.04 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_739E357D2F3D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Association between variants of the leptin receptor gene (LEPR) and overweight: a systematic review and an analysis of the CoLaus study.
Périodique
Plos One
Auteur(s)
Bender Nicole, Allemann Noëmi, Marek Diana, Vollenweider Peter, Waeber Gérard, Mooser Vincent, Egger Matthias, Bochud Murielle
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Statut éditorial
Publié
Date de publication
2011
Peer-reviewed
Oui
Volume
6
Numéro
10
Pages
e26157
Langue
anglais
Résumé
BACKGROUND: Three non-synonymous single nucleotide polymorphisms (Q223R, K109R and K656N) of the leptin receptor gene (LEPR) have been tested for association with obesity-related outcomes in multiple studies, showing inconclusive results. We performed a systematic review and meta-analysis on the association of the three LEPR variants with BMI. In addition, we analysed 15 SNPs within the LEPR gene in the CoLaus study, assessing the interaction of the variants with sex. METHODOLOGY/PRINCIPAL FINDINGS: We searched electronic databases, including population-based studies that investigated the association between LEPR variants Q223R, K109R and K656N and obesity- related phenotypes in healthy, unrelated subjects. We furthermore performed meta-analyses of the genotype and allele frequencies in case-control studies. Results were stratified by SNP and by potential effect modifiers. CoLaus data were analysed by logistic and linear regressions and tested for interaction with sex. The meta-analysis of published data did not show an overall association between any of the tested LEPR variants and overweight. However, the choice of a BMI cut-off value to distinguish cases from controls was crucial to explain heterogeneity in Q223R. Differences in allele frequencies across ethnic groups are compatible with natural selection of derived alleles in Q223R and K109R and of the ancient allele in K656N in Asians. In CoLaus, the rs10128072, rs3790438 and rs3790437 variants showed interaction with sex for their association with overweight, waist circumference and fat mass in linear regressions. CONCLUSIONS: Our systematic review and analysis of primary data from the CoLaus study did not show an overall association between LEPR SNPs and overweight. Most studies were underpowered to detect small effect sizes. A potential effect modification by sex, population stratification, as well as the role of natural selection should be addressed in future genetic association studies.
Mots-clé
Animals, Cohort Studies, Gene Frequency, Genotype, Humans, Overweight/genetics, Polymorphism, Single Nucleotide/genetics, Receptors, Leptin/genetics , Colaus Study
Pubmed
Web of science
Open Access
Oui
Création de la notice
27/10/2011 15:03
Dernière modification de la notice
20/08/2019 14:31
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