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A meta-analysis of associations of LEPR Q223R and K109R polymorphisms with Type 2 diabetes risk

BACKGROUND: Leptin receptor (LEPR) plays a pivotal role in the control of body weight, energy metabolism, and insulin sensitivity. Various genetic association studies were performed to evaluate associations of LEPR genetic variants with type 2 diabetes (T2D) susceptibility. METHODS: A comprehensive...

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Autores principales: Yang, Yunzhong, Niu, Tianhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749718/
https://www.ncbi.nlm.nih.gov/pubmed/29293570
http://dx.doi.org/10.1371/journal.pone.0189366
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author Yang, Yunzhong
Niu, Tianhua
author_facet Yang, Yunzhong
Niu, Tianhua
author_sort Yang, Yunzhong
collection PubMed
description BACKGROUND: Leptin receptor (LEPR) plays a pivotal role in the control of body weight, energy metabolism, and insulin sensitivity. Various genetic association studies were performed to evaluate associations of LEPR genetic variants with type 2 diabetes (T2D) susceptibility. METHODS: A comprehensive search was conducted to identify all eligible case-control studies for examining the associations of LEPR single nucleotide polymorphisms (SNPs) Q223R (rs1137101) and K109R (rs1137100) with T2D risk. Odds ratios (OR) and corresponding 95% confidence intervals (CIs) were used to measure the magnitudes of association. RESULTS: For Q223R, 13 studies (11 articles) consisting of a total of 4030 cases and 2844 controls, and for K109R 7 studies (7 articles) consisting of 3319 cases and 2465 controls were available. Under an allele model, Q223R was not significantly associated with T2D risk (OR = 1.09, 95% CI: 0.80–1.48, P-value = 0.5989), which was consistent with results obtained under four genotypic models (ranges: ORs 1.08–1.20, 95% CIs: 0.58–2.02 to 0.64–2.26; P-values, 0.3650–0.8177, which all exceeded multiplicity-adjusted α = 0.05/5 = 0.01). In addition, no significant association was found between K109R and T2D risk based on either an allele model (OR = 0.93, 95% CI: 0.85–1.03, P-value = 0.1868) or four genotypic models (ranges: ORs 0.81–0.99, 95% CIs: 0.67–0.86 to 0.97–1.26, P-values, 0.0207–0.8804 which all exceeded multiplicity-adjusted α of 0.01). The magnitudes of association for these two SNPs were not dramatically changed in subgroup analyses by ethnicity or sensitivity analyses. Funnel plot inspections as well as Begg and Mazumdar adjusted rank correlation test and Egger linear regression test did not reveal significant publication biases in main and subgroup analyses. Bioinformatics analysis predicted that both missense SNPs were functionally neutral and benign. CONCLUSIONS: The present meta-analysis did not detect significant genetic associations between LEPR Q223R and K109R polymorphisms and T2D risk.
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spelling pubmed-57497182018-01-26 A meta-analysis of associations of LEPR Q223R and K109R polymorphisms with Type 2 diabetes risk Yang, Yunzhong Niu, Tianhua PLoS One Research Article BACKGROUND: Leptin receptor (LEPR) plays a pivotal role in the control of body weight, energy metabolism, and insulin sensitivity. Various genetic association studies were performed to evaluate associations of LEPR genetic variants with type 2 diabetes (T2D) susceptibility. METHODS: A comprehensive search was conducted to identify all eligible case-control studies for examining the associations of LEPR single nucleotide polymorphisms (SNPs) Q223R (rs1137101) and K109R (rs1137100) with T2D risk. Odds ratios (OR) and corresponding 95% confidence intervals (CIs) were used to measure the magnitudes of association. RESULTS: For Q223R, 13 studies (11 articles) consisting of a total of 4030 cases and 2844 controls, and for K109R 7 studies (7 articles) consisting of 3319 cases and 2465 controls were available. Under an allele model, Q223R was not significantly associated with T2D risk (OR = 1.09, 95% CI: 0.80–1.48, P-value = 0.5989), which was consistent with results obtained under four genotypic models (ranges: ORs 1.08–1.20, 95% CIs: 0.58–2.02 to 0.64–2.26; P-values, 0.3650–0.8177, which all exceeded multiplicity-adjusted α = 0.05/5 = 0.01). In addition, no significant association was found between K109R and T2D risk based on either an allele model (OR = 0.93, 95% CI: 0.85–1.03, P-value = 0.1868) or four genotypic models (ranges: ORs 0.81–0.99, 95% CIs: 0.67–0.86 to 0.97–1.26, P-values, 0.0207–0.8804 which all exceeded multiplicity-adjusted α of 0.01). The magnitudes of association for these two SNPs were not dramatically changed in subgroup analyses by ethnicity or sensitivity analyses. Funnel plot inspections as well as Begg and Mazumdar adjusted rank correlation test and Egger linear regression test did not reveal significant publication biases in main and subgroup analyses. Bioinformatics analysis predicted that both missense SNPs were functionally neutral and benign. CONCLUSIONS: The present meta-analysis did not detect significant genetic associations between LEPR Q223R and K109R polymorphisms and T2D risk. Public Library of Science 2018-01-02 /pmc/articles/PMC5749718/ /pubmed/29293570 http://dx.doi.org/10.1371/journal.pone.0189366 Text en © 2018 Yang, Niu http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Yang, Yunzhong
Niu, Tianhua
A meta-analysis of associations of LEPR Q223R and K109R polymorphisms with Type 2 diabetes risk
title A meta-analysis of associations of LEPR Q223R and K109R polymorphisms with Type 2 diabetes risk
title_full A meta-analysis of associations of LEPR Q223R and K109R polymorphisms with Type 2 diabetes risk
title_fullStr A meta-analysis of associations of LEPR Q223R and K109R polymorphisms with Type 2 diabetes risk
title_full_unstemmed A meta-analysis of associations of LEPR Q223R and K109R polymorphisms with Type 2 diabetes risk
title_short A meta-analysis of associations of LEPR Q223R and K109R polymorphisms with Type 2 diabetes risk
title_sort meta-analysis of associations of lepr q223r and k109r polymorphisms with type 2 diabetes risk
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749718/
https://www.ncbi.nlm.nih.gov/pubmed/29293570
http://dx.doi.org/10.1371/journal.pone.0189366
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