Menopausal Status and MTHFR Gene Polymorphism in the Etiopathogenesis of Osteoporosis

Author(s): Yasovanthi Jeedigunta, Shehnaz Sultana, Balakrishna Nagalla, Raghunath Manchala, Rajender Rao Kalashikam

Background: Osteoporosis is a skeletal disorder characterized by low bone mass with consequent increase in bone fragility and fracture. The interplay between genetics and environment has a crucial role in determining the bone mineral density. Many studies showed that the genetic polymorphisms of MTHFR gene and its impact in the development of numerous human diseases. Normal MTHFR activity may help maintain the pool of circulating folate and methionine and possibly prevent of homocysteine. It has been shown that high serum homocysteine concentration may weaken bone by interfering with collagen cross-linking, thereby increasing the risk of osteoporosis. Therefore, the present study was aimed to investigate the role of MTHFR C677T gene polymorphism and its influence on BMD in pre and postmenopausal osteoporotic women of Indian ethnicity.

Methods: In this study 427 osteoporotic women and 460 age matched controls were included. MTHFR C677T gene polymorphism was assessed by PCR-RFLP method. Total ALP, Bone specific ALP Total acid phosphatase, TRAP, Calcium and Phosphorus was measured by Bergmeyer et al method.

Results: The frequency of TT genotype and T allele was more in pre- and postmenopausal osteoporotic women in comparison with controls. The logistic regression analysis to understand the risk assessment showed that the TT genotypes were 2.7 times (95% CI 1.1-1.6) and CT 1.7 times (95% CI 1.3-2.2 ) were at higher risk of osteoporosis in comparison to CC genotypes .This was found true even after adjustment for menopausal status.

Conclusions: This study showed that increased bone turnover is not only restricted to postmenopausal women indicating the role of MTHFR gene variations in determining osteoporosis in both pre and post-menopausal South Indian women from Telangana.