FTO gene associated fatness in relation to body fat distribution and metabolic traits throughout a broad range of fatness

Background

A common single nucleotide polymorphism (SNP) of FTO (rs9939609, T/A) is associated with total body fatness. We investigated the association of this SNP with abdominal and peripheral fatness and obesity-related metabolic traits in middle-aged men through a broad range of fatness present already in adolescence.

Methodology/Principal Findings

Obese young Danish men (n = 753, BMI≥31.0 kg/m²) and a randomly selected group (n = 879) from the same population were examined in three surveys (mean age 35, 46 and 49 years, respectively). The traits included anthropometrics, body composition, oral glucose tolerance test, blood lipids, blood pressure, fibrinogen and aspartate aminotransferase. Logistic regression analysis was used to assess the age-adjusted association between the phenotypes and the odds ratios for the FTO rs9939609 (TT and TA genotype versus the AA genotype), for anthropometrics and body composition estimated per unit z-score. BMI was strongly associated with the AA genotype in all three surveys: OR = 1.17, p = 1.1*10⁻⁶, OR = 1.20, p = 1.7*10⁻⁷, OR = 1.17, p = 3.4*10⁻³, respectively. Fat body mass index was also associated with the AA genotype (OR = 1.21, p = 4.6*10⁻⁷ and OR = 1.21, p = 1.0*10⁻³). Increased abdominal fatness was associated with the AA genotype when measured as waist circumference (OR = 1.21, p = 2.2*10⁻⁶ and OR = 1.19, p = 5.9*10⁻³), sagittal abdominal diameter (OR = 1.17, p = 1.3*10⁻⁴ and OR = 1.18, p = 0.011) and intra-abdominal adipose tissue (OR = 1.21, p = 0.005). Increased peripheral fatness measured as hip circumference (OR = 1.19, p = 1.3*10⁻⁵ and OR = 1.18, p = 0.004) and lower body fat mass (OR = 1.26, p = 0.002) was associated with the AA genotype. The AA genotype was significantly associated with decreased Stumvoll insulin sensitivity index (OR = 0.93, p = 0.02) and with decreased non-fasting plasma HDL-cholesterol (OR = 0.57, p = 0.037), but not with any other of the metabolic traits. However, all significant results for both body fat distribution and metabolic traits were explained by a mediating effect of total fat mass.

Conclusion

The association of the examined FTO SNP to general fatness throughout the range of fatness was confirmed, and this association explains the relation between the SNP and body fat distribution and decreased insulin sensitivity and HDL-cholesterol. The SNP was not significantly associated with other metabolic traits suggesting that they are not derived from the general accumulation of body fat.     

Novel genetic variants of sine oculis homeobox homolog 3 gene are associated with body weight and average daily gain in Bos taurus

Sine oculis homeobox homolog 3 (Six3) gene is responsible for normal mammalian pituitary development, and its genetic variations or deficiency will cause hypopituitarism, suggesting that this gene is a potential candidate gene for studying association with growth traits in animals. Herein, genetic variants within bovine Six3 gene was screened in 1031 individuals from four Chinese indigenous cattle breeds. Two novel polymorphisms (NC_007309:g.2515G>A and NC_007309:g.2607T>C) locating at positions nt1707 and nt1799 of intron 1 in bovine Six3 gene, were found, and could be genotyped by TaqI ACRS PCR-RFLP and Alw26I PCR-RFLP, respectively. The frequencies of allele “A” of TaqI locus varied from 0.004 to 0.309, as well as the frequencies of allele “C” of Alw26I locus waved from 0.025 to 0.340. Association analysis revealed no significant association of TaqI locus with growth traits in Nanyang breed. However, significant relationships between Alw26I locus and body weight (BW) and average daily gain (ADG) in Nanyang breed was found (p<0.05). The individuals with genotype TC had greater body weight and average daily gain than those with genotype TT at 18 months old. Furthermore, based on combinated genotypes from these two loci, diplotypes was found to be associated with growth traits (p<0.05).The individuals with dihaplotype GG-TC had greater body weight and average daily gain at 18 month-old than those of other dihaplotypes. Therefore, the TaqI and Alw26I genetic variants of bovine Six3 gene were recommended as DNA markers related to growth traits through marker-assisted selection for genetics and breeding in cattle.     

SNPs in the coding region of bovine MGAT2 gene are associated with body weight and weight gain

Monoacylglycerol acyltransferase 2 (MGAT2), as a candidate gene for quantitative traits, relates to dietary fat uptake, lipids synthesis and storage, which plays a major role in the absorption of dietary fat by catalyzing the resynthesis of triacylglycerol in enterocytes. In this study, based on DNA pool sequencing and PCR-RFLP methods, polymorphisms of the MGAT2 gene were detected in 1145 Chinese indigenous cattle. The results revealed two novel mutations located on exon 1 and exon 5 (NM_001099136.1:m.84G>T and 756A>G). Hence, we described the HaeIII forced PCR-RFLP method in exon1 and a MluI PCR-RFLP method in exon5 to detect them. In addition, the associations of these polymorphisms with growth traits were evaluated in Nanyang cattle. The results showed that only HaeIII locus was associated with body weight and average daily gain aged 6 months, and individuals with genotype TT showed significantly higher body weight and average daily gain than those with genotype GG.