Proopiomelanocortin gene variants are associated with serum leptin and body fat in a normal female population

Abstract

A major quantitative trait locus (QTL) determining leptin levels has been linked to the proopiomelanocortin (POMC) region on chromosome 2. Most studies, based on under 350 lean or obese subjects, have shown no association between POMC SNP 8246 C/T and serum leptin, but significant associations have been reported with RsaI 8246 C/T SNP haplotypes. We have investigated association of four POMC SNPs with body composition and serum leptin in 2758 normal Caucasian female subjects (mean age 47.4712.5 years), from the St Thomas' UK Adult Twin Registry (Twins UK): RsaI and 51 G/C in the 5 0 UTR and 8246 C/T and 7965 C/T in the 3 0 UTR. Under the recessive model, the 8246 T allele (freq. 0.18) was significantly associated with higher mean BMI (P ¼ 0.032) and total fat (P ¼ 0.046, both after age adjustment). Significant associations were maintained in sib-TDT with waist (P ¼ 0.049), total fat (P ¼ 0.037) and emerged with serum leptin (P ¼ 0.016). Initial significant associations between RsaI (À) allele (freq. 0.30) and higher waist (P ¼ 0.04) or % central fat (P ¼ 0.02) were not maintained in sib-TDT. No significant associations were found between body composition or serum leptin and RsaI/8246 C/T haplotype and none with 51 G/C (freq. 0.01) or 7965 C/T (freq. 0.004). There was minimal pairwise LD between the four loci, apart from RsaI and 8246 C/T (D 0 ¼ À0.78 (Po0.0001)). Associations of BMI, weight and total fat with SNPs in regions flanking the POMC gene in this powerful study suggest that regulation of POMC expression may be influential in determining body weight.

Association between rs155971 in the PCSK1 gene and the lipid profile of obese Thai children: a family-based study

“…The results of the present study differed from the family study in a white British population, which found an association between rs1042571 and WHR (Baker et al, 2005). Moreover, studies in the UK (Chen et al, 2005) and with Caucasian Americans (Wang et al, 2012) also found an association between rs1042571 and BMI. Baker et al (2005) found no association between rs1042571 and BMI in a white British population, which agrees with the present study.…”

“…The common variant C8246T (rs1042571), located in the 3'-untranslated region (UTR), was associated with waist-to-hip ratio (WHR) (P < 0.0001) in a family study on a white British population (Baker et al, 2005). Moreover, in the UK, this single nucleotide polymorphism (SNP) was associated with body mass index (BMI) (P = 0.032) and total fat (P = 0.046) in a recessive model (Chen et al, 2005). In Caucasian Americans, Wang et al (2012) found an association between the C8246T variant and BMI (overweight: P = 0.005; obese: P = 0.018; overweight + obese: P = 0.002) but not among African Americans.…”

Genetic relationships of body composition, serum leptin, and age at puberty in gilts12

“…Only 2 reports have identified age at puberty QTL in the pig (Rohrer et al, 1999;Cassady et al, 2001) on chromosomes 1, 7, 8, 10, and 12, and SNP in one of these regions on chromosome 10 are possibly associated (Nonneman et al, 2006) with age at puberty. The QTL for leptin concentrations in humans have been identified in the POMC gene, and SNP and POMC haplotypes are associated with circulating leptin, body mass index, BW, and body fat (Hixson et al, 1999;Chen et al, 2005). Liefers et al (2004) identified a polymorphism in LEPR associated with leptin concentration in pregnant heifers.…”

“…Polymorphisms in the leptin gene and leptin receptor have been associated with fatness traits, feed efficiency, and reproduction in pigs (Jiang and Gibson, 1999;Kennes et al, 2001;Chen et al, 2004;Mackowski et al, 2005). Genomic regions associated with age at puberty in the pig (Rohrer et al, 1999;Cassady et al, 2001) and leptin concentrations in mice and humans (Hixson et al, 1999;Harper et al, 2003;Chen et al, 2005) have been identified. Genetic relationships of fat and leptin with age at puberty may provide an alternative means of selecting for decreased age at puberty.…”

Associations between anthropometrical measurements, body composition, single-nucleotide polymorphisms of the hypothalamus/pituitary/adrenal (HPA) axis and HPA axis functioning

“…2 Supplementary support was found in our own observations, in which disturbance of HPA axis functioning under basal and challenged conditions was related to visceral fat accumulation. 8,9 Literature has also shown associations between the SNP BclI and HPA axis functioning; 10 for instance in men, the BclI GG genotype has been associated with increased salivary cortisol concentrations, particularly after stimulation by a standardized lunch, 4 increased cortisol concentrations after a 0AE5-mg dexamethasone suppression test, 4 and a diminished cortisol response to psychosocial stress. Literature has shown an association between common (minor allele frequency of at least 20%) SNPs of the HPA axis and obesity-related characteristics, such as the CG genotype of the glucocorticoid receptor gene (GR) referred to as the 'BclI' polymorphism (rs41423247).…”