Variation in the vitamin D receptor gene is associated with multiple sclerosis in an Australian population

Abstract

Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) resulting in accumulating neurological disability. The disorder is more prevalent at higher latitudes. Objectives: To investigate VDR gene variation using three intragenic restriction fragment length polymorphisms (Apa I, Taq I and Fok I) in an Australian MS case-control population. One hundred and four Australian MS patients were studied with patients classified clinically as Relapsing Remitting MS (RR-MS), Secondary Progressive MS (SP-MS) or Primary Progressive MS (PP-MS). Also, 104 age, sex and ethnicity matched controls were investigated as a comparative group. Our results show a significant difference of genotype distribution frequency between the case and control groups for the functional exon 9 VDR marker Taq I (PGen = 0.016) and interestingly, a stronger difference for the allelic frequency (PAll = 0.0072). The Apa I variant was also found to be associated with MS (PAll = 0.04) but genotype frequency was not significantly different from controls (PGen = 0.1). The Taq and Apa variants are in very strong and significant linkage disequilibrium (D'= 0.96, P < 0.0001) and their associations are more prominent with the progressive forms of MS (SP–MS and PP–MS). Neither of these two positive variants is in linkage disequilibrium with the negatively associated Fok I variant (PGen = 0.26; PAll = 0.218). Our results support a role for a susceptibility haplotype in the VDR gene increasing the risk of developing multiple sclerosis, particularly the progressive clinical subtypes of MS.