The FTO gene is associated with a paradoxically favorable cardiometabolic risk profile in frail, obese older adults

Pharmacogenet Genomics. 2016 Apr;26(4):154-160. doi: 10.1097/FPC.0000000000000201.


Objective: Fat mass and obesity-associated (FTO) gene polymorphisms have been reported to be associated with differences in BMI, obesity, and type 2 diabetes. However, previous studies have been predominantly conducted in younger individuals across a spectrum of body weights, whereas little information is available on the older population. We examined the association of FTO gene polymorphisms with cardiometabolic risks among adults who were both obese (BMI≥30 kg/m) and older (age≥65 years).

Methods: A total of 165 frail, obese older adults were genotyped for FTO (rs9939609 and rs8050136) single nucleotide polymorphisms and studied for associations with body weight and body composition, components and prevalence of the metabolic syndrome, insulin response to an oral glucose tolerance test, and levels of adipocytokines (e.g. leptin) and vitamin D.

Results: Carriers of the A allele (CA/AA) of the FTO single nucleotide polymorphism rs8050136 had lower body weight, BMI, body fat, and trunk fat than those without the A allele (CC genotype; all P's<0.05). Moreover, genotype CA/AA was associated with lower levels of triglycerides and higher levels of high-density lipoprotein-cholesterol and carriers of this genotype showed a trend toward a lower waist circumference, resulting in a lower prevalence of metabolic syndrome than in CC genotype carriers. The insulin area under the curve during the oral glucose tolerance test was lower for genotype CA/AA. Despite the lower insulin levels, the glucose area under the curve was unchanged, resulting in a higher insulin sensitivity index. Leptin levels were also lower and adiponectin and 25-hydroxyvitamin levels tended to be higher for genotype CA/AA than for genotype CC. No differences were observed for rs9939609.

Conclusion: Unlike the results from studies in younger individuals, the risk A allele may confer a favorable cardiometabolic risk profile in obese older adults, suggesting selective survival of obese adults into old age. If confirmed in a larger sample of surviving obese older adults, these findings may have implications in the clinical approach to obesity in this population.