SLC22A5 polymorphism associated with risk of extra-articular manifestations in rheumatoid arthritis patients

Rheumatoid arthritis (RA), the most common autoimmune disease, is thought to be a complex disease in which a combination of risk alleles from different susceptibility genes predisposes to development of the disease, following exposure to as yet unknown environmental factors. An important component of the carnitine system is the plasma membrane carnitine transporters, also called organic cation transporters, i.e. OCTN1 and OCTN2 encoded by the SLC22A4 and SLC22A5 genes, respectively. The aim of this study was to investigate the association between SLC22A5 polymorphism and RA.

The study was carried out on 404 patients diagnosed with RA according to the criteria of the American College of Rheumatology and 560 healthy subjects. The single nucleotide polymorphism (SNP) within the SLC22A5 gene - 207C>G (rs 2631367) was genotyped using pre-validated TaqMan genotyping assays.

The distribution of SLC22A5 genotypes and alleles in RA patients did not differ significantly from that in healthy controls. Moreover, there were no significant associations between SLC22A5 genotypes and age at time of disease diagnosis, rheumatoid factor, erosive disease and response to treatment with methotrexate. Extra-articular manifestations were diagnosed in 16.7% of SLC22A5 GG homozygous patients, in 9.4% with the GC genotype and in 7.2% of homozygous CC patients. The frequency of extra-articular manifestations was two-fold greater in homozygous GG patients as compared with carriers of the C allele (GG vs. GC + CC), OR = 2.06 (95% CI: 1.11-3.85, p = 0.022).

The results of the present study suggest that the SLC22A5 polymorphism may be associated with the development of extra-articular manifestations of RA but the distribution of SLC22A5 genotypes and alleles in studied RA patients did not significantly differ from healthy subjects.