VARIATION IN THE VITAMIN D RECEPTOR GENE IS ASSOCIATED WITH MULTIPLE SCLEROSIS IN AN AUSTRALIAN POPULATION

• Published in: Journal of neurogenetics Vol. 19; no. 1; pp. 25 - 38
• Main Authors: Tajouri, Lotti, Ovcaric, Micky, Curtain, Rob, Johnson, Matthew P., Griffiths, Lyn R., Csurhes, Peter, Pender, Michael P., Lea, Rod A.
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd 2005; Taylor & Francis
• Subjects: Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Linkage Disequilibrium; Male; Multiple Sclerosis - genetics; Polymorphism, Restriction Fragment Length; Receptors, Calcitriol - genetics; RFLP association; VDR gene
• ISSN: 0167-7063; 1563-5260
• DOI: 10.1080/01677060590949692

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. 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 alleles were also found to be associated with MS (pAll = 0.04) but genotype frequencies were 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). The genotypic associations are strongest for the progressive forms of MS (SP-MS and PP-MS). Our results support a role for the VDR gene increasing the risk of developing multiple sclerosis, particularly the progressive clinical subtypes of MS.