Abstract
Single nucleotide polymorphisms (SNPs) in the fat mass and obesity associated (FTO) gene are associated with body mass index (BMI) in populations of European descent. The FTO rs9939609 variant, first detected in a genome-wide association study of diabetes, conferred an increased disease risk that was abolished after adjustment for BMI, suggesting that the association may be due to variation in adiposity. The relationship between diabetes, four previously identified FTO polymorphisms that span a 19.6-kb genomic region, and obesity was therefore evaluated in the biracial population-based Atherosclerosis Risk in Communities Study with the goal of further refining the association by comparing results between the two ethnic groups. The prevalence of diabetes and obesity (BMI ≥30 kg/m2) was established at baseline, and diabetes was determined by either self-report, a fasting glucose level ≥126 mg/dL, or non-fasting glucose ≥200 mg/dL. There were 1,004 diabetes cases and 10,038 non-cases in whites, and 670 cases and 2,780 non-cases in African-Americans. Differences in mean BMI were assessed by a general linear model, and multivariable logistic regression was used to predict the risk of diabetes and obesity. For white participants, the FTO rs9939609 A allele was associated with an increased risk of diabetes (odds ratio (OR) = 1.19, p<0.001) and obesity (OR = 1.22, p<0.001) under an additive genetic model that was similar for all of the SNPs analyzed. In African-Americans, only the rs1421085 C allele was a determinant of obesity risk (OR = 1.17, p = 0.05), but was found to be protective against diabetes (OR = 0.79, p = 0.03). Adjustment for BMI did not eliminate any of the observed associations with diabetes. Significant statistical interaction between race and the FTO variants suggests that the effect on diabetes susceptibility may be context dependent.
Highlights
Diabetes is an important risk factor for cardiovascular disease [1]
There was a significant difference in the four fat mass and obesity associated (FTO) genotype frequencies between diabetes cases and non-cases found for whites, but a difference was only revealed for rs1421085 in African-Americans with the frequency of the minor allele higher in non-cases than in cases
In contrast to the results described above for whites, three of the FTO SNPs were not significantly associated with diabetes case status for African-American participants in the Atherosclerosis Risk in Communities (ARIC) study (Table 5)
Summary
Diabetes is an important risk factor for cardiovascular disease [1]. Obesity is an independent risk factor for diabetes [2] and either BMI or waist-to-hip ratio (WHR) has been commonly used as a surrogate measure of adiposity. Genetic variants in FTO have been reported to be associated with BMI in study populations of European descent [4,5,6,7,8], functional polymorphisms in this gene have not yet been identified. FTO is ubiquitously expressed in human tissues [6,7], with a high level found in the hypothalamus indicating a possible role in the regulation of appetite or energy balance In accordance with this hypothesis, introduction of a Fto null mutation in mice resulted in postnatal growth retardation, loss of white adipose tissue, and increased energy expenditure [9]. To date there have been no investigations of the association between FTO variants and diabetes or obesity in a community-based study that included both African-American men and women
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
