ABSTRACT
BACKGROUND: The prevalence of childhood obesity has been dramatically increasing in developing countries as it has been reported for developed nations. Identifying susceptibility genes in early life could provide the foundations for interventions in lifestyle to prevent obese children to become obese adults. OBJECTIVES: The objective of this study was to evaluate the influence of genetic variants related to obesity identified by genome-wide association studies (MC4R, TMEM18, KCTD15, SH2B1, SEC16B, BDNF, NEGR1, OLFM4 and HOXB5 genes) on anthropometric and dietary phenotypes in two Brazilian cohorts followed-up since birth. METHODS: There were 745 children examined at birth, after 1 year and after 3.5 years of follow-up. Ten single nucleotide polymorphisms were genotyped. Anthropometric and dietary parameters were compared among genotypes. Children were classified as overweight when body mass index Z-score was >+1. RESULTS: Overweight prevalence was 30.7% at 3.5 years old. Significant associations were identified at 3.5 years old for TMEM18 rs6548238, NEGR1 rs2815752, BDNF rs10767664 and rs6265 (1 year old and 3.5 years old) with anthropometric phenotypes and at 3.5 years old for SEC16B rs10913469 with dietary parameters. CONCLUSIONS: Our results indicate that genetic variants in/near these genes contribute to obesity susceptibility in childhood and highlight the age at which they begin to affect obesity-related phenotypes.
Subject(s)
Brain-Derived Neurotrophic Factor/genetics , Cell Adhesion Molecules, Neuronal/genetics , DNA-Binding Proteins/genetics , Membrane Proteins/genetics , Overweight/genetics , Pediatric Obesity/genetics , Adult , Body Mass Index , Brazil , Child , Child, Preschool , Cohort Studies , Female , GPI-Linked Proteins/genetics , Genetic Predisposition to Disease , Genetic Variation , Genome-Wide Association Study , Genotype , Humans , Infant , Male , Overweight/epidemiology , Pediatric Obesity/epidemiology , Polymorphism, Single NucleotideABSTRACT
Endogenous and exogenous sex steroid hormones have multiple effects on lipid and lipoprotein metabolism. It is also known that estrogen has antiatherogenic actions, therefore we considered examining whether there was any association between polymorphisms in estrogen-metabolizing genes and lipid levels in women. We investigated the association between variants in genes related to estrogen biosynthesis (CYP19-TTTA(n)) and estrogen catabolism (CYP1A1*2A, CYP1A1*2C, CYP1A2-Asn516Asn, CYP3A4*1B, and COMT-Val158Met) with serum lipid levels in a cross-sectional study with 472 Brazilian women of European descent. They were divided into three subgroups according to their hormonal status: premenopausal women (n=187), postmenopausal women exposed to hormonal replacement therapy (HRT) (n=118), and postmenopausal women unexposed to HRT (n=167). The postmenopausal women receiving HRT who were carriers of the CYP3A4*1B variant showed lower low-density lipoprotein cholesterol levels than wild-type homozygotes. Premenopausal women homozygous for the CYP1A1*2C allele had higher high-density lipoprotein cholesterol levels than heterozygotes. While the CYP1A1*2C variant probably has a higher catalytic activity, the functional implications of the CYP3A4 polymorphism are still uncertain. These data are the first attempt to associate estrogen metabolism genes to lipid levels in women.
Subject(s)
Cytochrome P-450 Enzyme System/genetics , Estrogen Replacement Therapy , Estrogens/metabolism , Lipoproteins, HDL/blood , Polymorphism, Genetic , Postmenopause/genetics , Premenopause/genetics , Adolescent , Adult , Aromatase/genetics , Catechol O-Methyltransferase/genetics , Cytochrome P-450 CYP1A1/genetics , Cytochrome P-450 CYP1A2/genetics , Cytochrome P-450 CYP3A , Female , Gene Frequency , Humans , Middle AgedABSTRACT
Sex steroid hormones have multiple effects on lipid metabolism. We investigated the association between two common single nucleotide polymorphisms of the estrogen receptor 2 gene (ESR2), 1082G>A and 1730A>G, and PROGINS polymorphism of the progesterone receptor gene (PGR) with lipoprotein levels in a cross-sectional study with 472 women of European descent. The women were classified into three subgroups according to hormonal status, premenopausal women (n=187; mean age=34+/-9.7 years), postmenopausal women exposed to hormone replacement therapy (HRT) (n=118; 56+/-6.7 years) and postmenopausal women unexposed to HRT (n=167; 58+/-9.8 years). The premenopausal and postmenopausal women exposed to HRT, both carriers of G/A genotype, exhibited LDL-C (P=0.027 and 0.001, respectively) and T-chol levels (P=0.035 and 0.001, respectively) lower than carriers of G/G genotype. This association was not observed in postmenopausal women unexposed to HRT. These results suggest that ESR2 1082G>A genotype may influence LDL-C levels in women with abundant estrogen levels, due to either endogenous or exogenous sources.
