Effect of genetic variation in the leptin gene promoter and the leptin receptor gene on obesity risk in a population-based case-control study in Spain

Abstract

There are no good genetic markers for incorporating the study of genetic susceptibility to obesity in epidemiological studies. In animal models, the leptin (LEP) and the leptin receptor (LEPR) genes have been shown to be very important in obesity because leptin functions as a negative feedback signal in regulating body-weight through reducing food intake and stimulating energy expenditure. In humans, several polymorphisms in these genes have been described. However, their association with obesity is still very controversial because there are no good case-control studies designed to specifically test this association. Our objective has been to conduct a population-based case-control study to estimate the risk of obesity arising from the -2548G > A and Q223R polymorphisms in the LEP and LEPR genes, respectively. 303 obese cases (101 men and 202 women) and 606 controls (202 men and 404 women) were selected from a Spanish Mediterranean population. Genetic, clinical and life-style characteristics were analyzed. No association was found between the -2548G > A polymorphism and obesity. However, the Q223R variant was significantly associated with obesity in a recessive model, the RR genotype being more prevalent in controls than in obese subjects. The inverse association between the Q223R polymorphism and obesity (OR = 0.62; 95% CI: 0.39-0.99) remained significant even after additional adjustment for education, tobacco smoking, alcohol, physical activity, origin of the obese patient, and the -2548G > A polymorphism in the LEP gene (OR = 0.54; 95% CI: 0.32-0.89). In conclusion, the -2548G > A polymorphism is not a relevant obesity marker in this Mediterranean population, although Q223R does seen to be so.

Common SNPs in LEP and LEPR associated with birth weight and type 2 diabetes-related metabolic risk factors in twins

“…In literature, both alleles of these SNPs have been reported as risk alleles for type 2 diabetes and obesity, and a metaanalytic study reported nonsignificant associations. [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]48 Consequently, additional studies in larger populations need to be carried out, to verify the involvement of these coding LEPR SNPs in the 'fetal insulin hypothesis'.…”

“…In this study we therefore examined the effect of common SNPs in LEP and LEPR on birth weight and adult metabolic risk factors for type 2 diabetes measured in young twins recruited from the East Flanders Prospective Twin Survey (EFPTS). The SNPs studied have previously been associated with type 2 diabetesrelated traits in other populations, [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] and are either nonsynonymous or located in a region that might be of importance in the regulation of gene expression.…”

Genome-wide scan revealed genetic loci for energy metabolism in Hispanic children and adolescents

“…Leptin regulates body weight through reducing food intake and stimulating energy expenditure. Polymorphisms in the LEPR gene may contribute to weight gain in young Dutch, 31 resting metabolic rate and substrate oxidation during low-intensity exercise in Canadians, 32 obesity in a Mediterranean 33 and Brazilian populations, 34 and 24-h TEE in Pima Indians. 35 Our signal on chromosome 9 for PROOX duplicates previous genetic findings related to obesity.…”

Is the time right for translation research in genomics?

“…Genetic associations may not only differ between ethnic groups, but also within. In Europe, there may be differences in genetic and other risk factors between northern and southern countries (e.g., multiple sclerosis, breast and other cancers, lipids), which asks for gene-disease association studies in specific populations, e.g., [16,17] also because true genetic heterogeneity between populations may later impact the global applicability of predictive genetic tests. Because gene-gene and geneenvironment interactions have not been extensively studied to date, further major advances in unraveling the genetic basis of common diseases may certainly be expected.…”