Analysis of Cdx2 VDR gene polymorphism rs11568820 in association with multiple sclerosis in Slovaks

• Published in: Neurological research (New York) 2023-10, Vol.45 (10), p.1-918
• Main Authors: Čierny, Daniel, Dobrota, Dušan, Kantorová, Ema, Malicherová, Bibiana, Škereňová, Mária, Javor, Juraj, Kurča, Egon, Lehotský, Ján
• Format: Article
• Language: English
• ISSN: 0161-6412; 1743-1328
• DOI: 10.1080/01616412.2023.2247195

Vitamin D deficiency is involved in the pathogenesis of multiple sclerosis (MS), a severe autoimmune demyelinating disease of the central nervous system. The gene polymorphism Cdx-2 (rs11568820, G/A) seriously influences the trancriptional activity of the vitamin D receptor (VDR) that binds the vitamin D responsive elements of target genes including HLA-DRB1*15. The aim of the present study in Slovaks was to analyse the association of Cdx-2 variants with the risk of MS and disability progression, and to assess the DRB1*15:01 allele as a possible confounding factor. In total, 493 MS patients and 417 healthy controls were involved in this study. The genotyping of Cdx-2 was performed using restriction analysis; DRB1*15:01 positivity was determined by a high-resolution melting analysis of its surrogate marker rs3135388 (G/A). Our results did not prove any allelic association between Cdx-2 and a risk of MS (minor allele A - 0.181 in patients vs. 0.161 in controls, OR = 1.15, .95 CI = 0.90-1.47,  = 0.289). The logistic regression analysis, adjusted for sex and age, showed no differences in Cdx-2 genotype counts when using an additive, dominant or recessive genetic model (  = 0.351, 0.150, 0.240 respectively). The Cdx-2 variants were also not associated with disease disability progression, evaluated using the Multiple Sclerosis Severity Score. The HLA-DRB1*15:01 allele was found to strongly increase the risk of MS in our study (0.300 in patients vs. 0.101 in controls, OR = 3.83, .95 CI = 2.94-4.99,  = 1.016 × 10 , dominant genetic model OR = 4.62, .95 CI = 3.40-6.26,  = 9.1 × 10 ). In summary, we found the Cdx-2 as a single genetic marker not to be associated with MS development or progression in Slovaks, independently of HLA-DRB1*15:01 status.