Contribution of Common Genetic Variants to Obesity and Obesity-Related Traits in Mexican Children and Adults

Abstract

BackgroundSeveral studies have identified multiple obesity-associated loci mainly in European populations. However, their contribution to obesity in other ethnicities such as Mexicans is largely unknown. The aim of this study was to examine 26 obesity-associated single-nucleotide polymorphisms (SNP) in a sample of Mexican mestizos.Methods9 SNPs in biological candidate genes showing replications (PPARG, ADRB3, ADRB2, LEPR, GNB3, UCP3, ADIPOQ, UCP2, and NR3C1), and 17 SNPs in or near genes associated with obesity in first, second and third wave GWAS (INSIG2, FTO, MC4R, TMEM18, FAIM2/BCDIN3, BDNF, SH2B1, GNPDA2, NEGR1, KCTD15, SEC16B/RASAL2, NPC1, SFRF10/ETV5, MAF, PRL, MTCH2, and PTER) were genotyped in 1,156 unrelated Mexican-Mestizos including 683 cases (441 obese class I/II and 242 obese class III) and 473 normal-weight controls. In a second stage we selected 12 of the SNPs showing nominal associations with obesity, to seek associations with quantitative obesity-related traits in 3 cohorts including 1,218 Mexican Mestizo children, 945 Mexican Mestizo adults, and 543 Indigenous Mexican adults.ResultsAfter adjusting for age, sex and admixture, significant associations with obesity were found for 6 genes in the case-control study (ADIPOQ, FTO, TMEM18, INSIG2, FAIM2/BCDIN3 and BDNF). In addition, SH2B1 was associated only with class I/II obesity and MC4R only with class III obesity. SNPs located at or near FAIM2/BCDIN3, TMEM18, INSIG2, GNPDA2 and SEC16B/RASAL2 were significantly associated with BMI and/or WC in the combined analysis of Mexican-mestizo children and adults, and FTO locus was significantly associated with increased BMI in Indigenous Mexican populations.ConclusionsOur findings replicate the association of 8 obesity-related SNPs with obesity risk in Mexican adults, and confirm the role of some of these SNPs in BMI in Mexican adults and children.

Polymorphisms FTO rs9939609, PPARG rs1801282 and ADIPOQ rs4632532 and rs182052 but not lifestyle are associated with obesity related-traits in Mexican children

“…Waist/height ratio measures the abdominal fat in any gender or age and is a better metabolic risk predictor than BMI (Browning et al , 2010; Kodama et al , 2012). This result is in agreement with other studies in different populations (León-Mimila et al , 2013; Luczynski et al , 2012; Villalobos-Comparán et al , 2008; Xi et al , 2010). We also found that the A allele increases the risk of alterations in the lipid profile (cholesterol and HDL levels), as reported by other groups (Villalobos-Comparán et al , 2008; Mascarenhas-Melo et al , 2013).…”

Interactions between uncoupling protein 2 gene polymorphisms, obesity and alcohol intake on liver function: a large meta-analysed population-based study

“…These polymorphisms have been shown to be associated with various metabolic traits such as obesity (24), body fat distribution (25), resting energy expenditure (26), type 2 diabetes (10) and insulin resistance (9,27) in various populations from different ethnic backgrounds (24). However, there were also studies that failed to show an association between these polymorphisms and metabolic traits (8,28,29). These inconsistencies could be attributed to the small sample size, incomplete coverage of the UCP2 gene variations or potential population-specific influences on metabolic traits (29).…”

Genes regulated by potassium channel tetramerization domain containing 15 (Kctd15) in the developing neural crest

“…Mutations in KCTD1 in humans are responsible for scalp-ear-nipple (SEN) syndrome (Marneros et al, 2013), but it is not known whether inhibition of AP-2 or Wnt signaling plays a role in the etiology of this disease. KCTD15 is not been reported as the cause of a disease, but numerous studies show an association between this gene and obesity (Gutierrez-Aguilar et al, 2012; Leon-Mimila et al, 2013; Mei et al, 2012; Willer et al, 2009; Williams et al, 2012). It is known that AP-2α regulates the activity of C/EBPα during adipogenesis (Jiang et al, 1998), and AP-2β affects other steps of adipogenesis and insulin resistance (Ikeda et al, 2006; Meng et al, 2010; Tao et al, 2006; Zhang et al, 2014).…”