Single nucleotide variants around the connective tissue growth factor (CTGF/CCN2) gene and their association with multiple sclerosis risk, disability scores, and rate of disease progression

Background This study aimed to explore the possible association of single nucleotide polymorphisms (SNPs) in the upstream (rs9402373) and downstream regions (rs9399005 and rs12526196) of the gene encoding connective tissue growth factor ( CTGF / CCN2 ) with relapsing–remitting multiple sclerosis (RRMS) risk and clinical parameters including disability scores and rate of disability progression. Materials and methods In total, 200 patients with RRMS and 305 controls were genotyped using real-time PCR (rs1252696 C/T and rs9402373 G/C) or PCR–RFLP (rs9399005 C/T) methods. Furthermore, the association between these genotypes and clinical parameters including Expanded Disability Status Scale (EDSS) score, Multiple Sclerosis Severity Score (MSSS), age at onset, duration of disease, duration of treatment, and presence of contrast-enhancing lesions was analyzed. Results rs9399005 genotypes TT and CT in the dominant model were significant predictors of RRMS vs. control status by logistic regression analysis (OR = 1.45, 95% CI = 1.01–2.08, P = .04). Moreover, these genotypes for rs9399005 were associated with a MSSS ≥ 2.4 (OR = 3.54, 95% CI = 1.56–8.05, P = .003). In addition, MSSS was lower in patients who had at least one rs12526196C allele than in the corresponding patients with the TT genotype ( P = .02). Conclusion To our knowledge, this is the first evidence of the involvement of variants around the CTGF gene in MS risk and disability progression.