Genetic Polymorphisms in the ESR1 and VDR Genes Do Not Correlate With Osteoporosis in Patients With Familial Dysautonomia

One of the major clinical manifestations of familial dysautonomia (FD)—a rare, neurodegenerative, autosomal-recessive disorder—is a high incidence and early onset of osteoporotic bone fractures. Early diagnosis is essential to initiate preventative therapy in at-risk patients and thus improve quality of life. However, the current lack of understanding of the complex relationship between FD and osteoporosis etiology precludes early diagnosis, and as such, accurate predictors of osteoporosis development in FD patients remain to be determined. It has been previously reported that a restriction fragment length polymorphism in the gene encoding the vitamin D receptor (VDR) and the number of thymine-adenine (TA) repeats in the gene encoding the estrogen receptor alpha (ESR1) may each be associated with determinants of bone mineral density and may thus predict the development of osteoporosis across a number of non-FD populations. In this study, we aimed to examine the correlation between osteoporosis and the presence of these genetic polymorphisms and to establish whether they could be used as predictive markers of osteoporosis development in the context of FD. The correlations between osteoporosis and either the BsmI restriction site polymorphism in VDR or the (TA)n repeat polymorphism in ESR1 were analyzed in 73 and 67 genotyped patients, respectively. Osteoporosis was defined as a bone mineral density greater than 2.5 (T-score) or greater than 2 (Z-score) standard deviations below the mean, as measured by dual-energy X-ray absorptiometry of the spine or hip. In both instances, no statistically significant difference in the frequency of polymorphism could be detected between FD patients with and without osteoporosis. Neither polymorphism can serve as a predictive marker for the development of osteoporosis in FD patients.