CD226 rs763361:C>T polymorphism is associated with multiple sclerosis risk independently of HLA-DRB1*15:01 allele and sex

OBJECTIVES: The rs763361:C>T (Gly307Ser) polymorphism in the cluster of differentiation 226 (CD226) gene has been implicated in susceptibility to multiple sclerosis (MS) and other autoimmune diseases; however, the results have been controversial and inconclusive. This study aimed to 1) investigate the association of rs763361 with MS susceptibility in Slovaks using a case-control approach, 2) conduct a meta-analysis of available data from different populations to validate this effect, 3) assess the interaction of rs763361 with major MS risk allele HLA-DRB1*15:01 allele and sex, and 4) analyse its correlation with clinical parameters of disease severity and progression. METHODS: CD226 rs763361 was genotyped in 558 MS patients and 1,101 controls by a polymerase chain reaction-restriction fragment length polymorphism method. Its association with MS risk and clinical parameters was analysed by logistic and linear regression analyses. In addition, a meta-analysis including six independent studies was subsequently performed. RESULTS: Statistical analysis revealed a significantly increased risk of developing MS for rs763361 T allele in allelic (P = 0.036; OR = 1.17; 95% CI = 1.01-1.35) and other genetic models, irrespective of the carrier status of HLA-DRB1*15:01 or sex. This association was subsequently confirmed in a meta-analysis. On the other hand, no association of rs763361 could be found with age at disease onset, MS severity score (MSSS), and progression index (PI). CONCLUSION: Our results demonstrate that CD226 rs763361 polymorphism confers susceptibility to MS but seems not to affect age of its onset, severity, or rate of disability accumulation.