Charita Koya1, Tsung Yu2, Carol Strong2, Meng-Che Tsai3. 1. 1 Faculty of Health Sciences, University of Ottawa , Ottawa, Ontario, Canada . 2. 2 Department of Public Health, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University , Tainan, Taiwan . 3. 3 Division of Genetics, Endocrinology, and Metabolism, Department of Pediatrics, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University , Tainan, Taiwan .
Abstract
BACKGROUND: Two common missense variants in the melanocortin-3 receptor (MC3R) gene, Thr6Lys (T6K) and Val81Ile (V81I), are presumably correlated with pediatric obesity. This meta-analysis aimed to examine and synthesize evidence on the association between these two common MC3R polymorphisms and the development of childhood obesity. METHODS: A combination of words relevant to the research question was searched on PubMed, EMBASE, Scopus, and the Cochrane database. Results were restricted to human studies, specifically child and adolescent populations. Articles were excluded based on accessibility of full online texts and availability of pertinent data. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random effects model to determine the association of the polymorphisms with obesity. RESULTS: Searches on the databases using the keywords identified 65 potentially relevant reports. Among them, 32 studies were excluded due to irrelevance, and 28 studies excluded due to lack of access, insufficient data, and investigation of other variants. A final set of five studies included in this meta-analysis found that the risk of overweight/obesity increased by 46.1% per K allele and 21.7% per I allele. Only homozygous genotypes for T6K were associated with a 3.10-fold (95% CI: 1.29-7.43) increased risk of overweight/obesity in children. Data were insufficient to examine if homozygosity for both rare alleles further increases risk. CONCLUSIONS: Our results supported a recessive inheritance model for MC3R gene as a potential cause of childhood obesity. High clinical heterogeneity existed among studies and thus requires more research of larger participation for future integration of data.
BACKGROUND: Two common missense variants in the melanocortin-3 receptor (MC3R) gene, Thr6Lys (T6K) and Val81Ile (V81I), are presumably correlated with pediatric obesity. This meta-analysis aimed to examine and synthesize evidence on the association between these two common MC3R polymorphisms and the development of childhood obesity. METHODS: A combination of words relevant to the research question was searched on PubMed, EMBASE, Scopus, and the Cochrane database. Results were restricted to human studies, specifically child and adolescent populations. Articles were excluded based on accessibility of full online texts and availability of pertinent data. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random effects model to determine the association of the polymorphisms with obesity. RESULTS: Searches on the databases using the keywords identified 65 potentially relevant reports. Among them, 32 studies were excluded due to irrelevance, and 28 studies excluded due to lack of access, insufficient data, and investigation of other variants. A final set of five studies included in this meta-analysis found that the risk of overweight/obesity increased by 46.1% per K allele and 21.7% per I allele. Only homozygous genotypes for T6K were associated with a 3.10-fold (95% CI: 1.29-7.43) increased risk of overweight/obesity in children. Data were insufficient to examine if homozygosity for both rare alleles further increases risk. CONCLUSIONS: Our results supported a recessive inheritance model for MC3R gene as a potential cause of childhood obesity. High clinical heterogeneity existed among studies and thus requires more research of larger participation for future integration of data.
Authors: Jonathan P Bradfield; Suzanne Vogelezang; Janine F Felix; Alessandra Chesi; Øyvind Helgeland; Momoko Horikoshi; Ville Karhunen; Estelle Lowry; Diana L Cousminer; Tarunveer S Ahluwalia; Elisabeth Thiering; Eileen Tai-Hui Boh; Mohammad H Zafarmand; Natalia Vilor-Tejedor; Carol A Wang; Raimo Joro; Zhanghua Chen; William J Gauderman; Niina Pitkänen; Esteban J Parra; Lindsay Fernandez-Rhodes; Akram Alyass; Claire Monnereau; John A Curtin; Christian T Have; Shana E McCormack; Mette Hollensted; Christine Frithioff-Bøjsøe; Adan Valladares-Salgado; Jesus Peralta-Romero; Yik-Ying Teo; Marie Standl; Jaakko T Leinonen; Jens-Christian Holm; Triinu Peters; Jesus Vioque; Martine Vrijheid; Angela Simpson; Adnan Custovic; Marc Vaudel; Mickaël Canouil; Virpi Lindi; Mustafa Atalay; Mika Kähönen; Olli T Raitakari; Barbera D C van Schaik; Robert I Berkowitz; Shelley A Cole; V Saroja Voruganti; Yujie Wang; Heather M Highland; Anthony G Comuzzie; Nancy F Butte; Anne E Justice; Sheila Gahagan; Estela Blanco; Terho Lehtimäki; Timo A Lakka; Johannes Hebebrand; Amélie Bonnefond; Niels Grarup; Philippe Froguel; Leo-Pekka Lyytikäinen; Miguel Cruz; Sayuko Kobes; Robert L Hanson; Babette S Zemel; Anke Hinney; Koon K Teo; David Meyre; Kari E North; Frank D Gilliland; Hans Bisgaard; Mariona Bustamante; Klaus Bonnelykke; Craig E Pennell; Fernando Rivadeneira; André G Uitterlinden; Leslie J Baier; Tanja G M Vrijkotte; Joachim Heinrich; Thorkild I A Sørensen; Seang-Mei Saw; Oluf Pedersen; Torben Hansen; Johan Eriksson; Elisabeth Widén; Mark I McCarthy; Pål R Njølstad; Christine Power; Elina Hyppönen; Sylvain Sebert; Christopher D Brown; Marjo-Riitta Järvelin; Nicholas J Timpson; Stefan Johansson; Hakon Hakonarson; Vincent W V Jaddoe; S F A Grant Journal: Hum Mol Genet Date: 2019-10-01 Impact factor: 6.150