Abstract
The “male-female health-survival paradox” evidences that the survival advantage observed in women is linked to higher rates of disability and poor health status compared to men, a phenomenon also called the “sex-frailty paradox”. The depletion of vitamin D seems to play a role in the fragilization of old persons, and genetic polymorphisms of the vitamin D receptor (VDR) gene seem to be involved in regulating the vitamin D pathway. This study correlated the VDR gene polymorphisms (FokI, ApaI, BsmiI, and TaqI) with frailty, computed by frailty index (FI), in 202 persons (127 women and 75 men, aged from 60 to 116 years), aiming to capture the involvement of vitamin D in the sex-frailty paradox. The results showed slightly higher FI (p = 0.05), lower levels of 25(OH)D (p = 0.04), and higher levels of parathyroid hormone PTH (p = 0.002) and phosphorus (p < 0.001) in women than in men. Interestingly, the ApaI minor allele (Aa + aa) showed a significant positive association with FI (p = 0.03) and a negative association with inorganic phosphorus values (p = 0.04) compared to AA genotype only in women, regardless of age. The exact mechanism and the causal role that, in old women, links ApaI polymorphism with frailty are still unclear. However, we could speculate that a specific genetic profiling, other than 25(OH)D levels, play a role in the sex-frailty paradox.
Highlights
The worldwide increase of human life expectancy and the concomitant rapid aging of the population represent major demographic phenomena of the last century.It has been known that aging has different effects in women and men: a phenomenon described as the “male-female health-survival paradox”, known as the “sex-frailty paradox” [1], in which women experience greater longevity than men [2]
The sex-frailty paradox has recently been explained with the proposal that women may experience a different kind of frailty: though they manifest a poorer health status compared to men, such higher vulnerability does not translate into a higher risk of death [4,5,6]
Linkage disequilibrium and haplotype gender association were calculated by SHEsis [18] and haplotype correlation with frailty index (FI) as well as with biochemical parameters was calculated by regression analysis, adjusting by age, using PLINK software [19]
Summary
The worldwide increase of human life expectancy and the concomitant rapid aging of the population represent major demographic phenomena of the last century. In a cohort study of centenarians we have previously identified an association between these SNPs with functional, physical, and cognitive performances [14] In this cohort, certain genetic profiles were related to different prevalence of age-related diseases, such as hypertension, acute myocardial infarction, angina, venous insufficiency, dementia, chronic obstructive pulmonary disease, and arthrosis [14]. Starting from these premises, we analyzed possible associations between frailty and the vitamin D pathway as well as VDR gene profiling in a cohort of very old women and men. We used the frailty index (FI) as measure of frailty because it is designed to estimate the biological aging of the individual through a quantitative (i.e., the age-related accumulation of health deficits) [15] and multidimensional [16] approach
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