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

<h4>Background</h4>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-...

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Autores principales:	Nicole Bender, Noëmi Allemann, Diana Marek, Peter Vollenweider, Gérard Waeber, Vincent Mooser, Matthias Egger, Murielle Bochud
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3ac75fc1a5af4087876ced809c18371c
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spelling	oai:doaj.org-article:3ac75fc1a5af4087876ced809c18371c2021-11-18T07:36:19ZAssociation between variants of the leptin receptor gene (LEPR) and overweight: a systematic review and an analysis of the CoLaus study.1932-620310.1371/journal.pone.0026157https://doaj.org/article/3ac75fc1a5af4087876ced809c18371c2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22028824/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions</h4>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.Nicole BenderNoëmi AllemannDiana MarekPeter VollenweiderGérard WaeberVincent MooserMatthias EggerMurielle BochudPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 10, p e26157 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nicole Bender Noëmi Allemann Diana Marek Peter Vollenweider Gérard Waeber Vincent Mooser Matthias Egger Murielle Bochud Association between variants of the leptin receptor gene (LEPR) and overweight: a systematic review and an analysis of the CoLaus study.
description	<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions</h4>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.
format	article
author	Nicole Bender Noëmi Allemann Diana Marek Peter Vollenweider Gérard Waeber Vincent Mooser Matthias Egger Murielle Bochud
author_facet	Nicole Bender Noëmi Allemann Diana Marek Peter Vollenweider Gérard Waeber Vincent Mooser Matthias Egger Murielle Bochud
author_sort	Nicole Bender
title	Association between variants of the leptin receptor gene (LEPR) and overweight: a systematic review and an analysis of the CoLaus study.
title_short	Association between variants of the leptin receptor gene (LEPR) and overweight: a systematic review and an analysis of the CoLaus study.
title_full	Association between variants of the leptin receptor gene (LEPR) and overweight: a systematic review and an analysis of the CoLaus study.
title_fullStr	Association between variants of the leptin receptor gene (LEPR) and overweight: a systematic review and an analysis of the CoLaus study.
title_full_unstemmed	Association between variants of the leptin receptor gene (LEPR) and overweight: a systematic review and an analysis of the CoLaus study.
title_sort	association between variants of the leptin receptor gene (lepr) and overweight: a systematic review and an analysis of the colaus study.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/3ac75fc1a5af4087876ced809c18371c
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Association between variants of the leptin receptor gene (LEPR) and overweight: a systematic review and an analysis of the CoLaus study.

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