Gender-specific association between FSHR and PPARG common variants and human longevity

Men and women have different life expectancies. Not unexpectedly, several genes involved in life span determination have been found to influence the probability of achieving longevity differently in men and women. This investigation examines the association between longevity and polymorphisms of follicle-stimulating hormone receptor (FSHR, Asn680Ser polymorphism) and peroxisome proliferator-activated receptor gamma (PPARG, Pro12Ala polymorphism), two genes that previous investigations suggested may exert a gender-specific influence on human longevity. A sample of 277 individuals (mean age, 82.9±5.7years) was recruited in 2000. On the basis of mortality data collected in 2009, the sample was divided into two groups of subjects surviving over 90 years (long-lived) or not (controls). The frequency of the FSHR 680 Ser/Ser genotype was significantly higher in the sample of long-lived women compared to controls, indicating that the FSHR 680 Ser/Ser genotype may favor survival to more than 90 years of age only in women (odds ratio [OR]=4.21; 95% confidence interval [CI], 1.10-16.10, p=0.036). In contrast, the frequency of the PPARG Pro/Ala genotype was significantly higher in the sample of male subjects who died before 90 years of age than in the long-lived, suggesting that carrying the PPARG Pro/Ala genotype may prevent the attainment of advanced age only in men (OR=0.13; 95% CI, 0.02-0.79; p=0.03). We then searched the literature for studies reporting a differential role for the genetic component in male and female longevity. To do this, we selected longevity genes with a gender-specific effect. A review of the studies showed that genetic factors tend to have a greater relevance in determining longevity in men than in women. The possible impact of this phenomenon is discussed.