Association of C1q gene cluster variants with rheumatoid arthritis: a pilot study

Single-nucleotide polymorphisms (SNPs) in C1q gene cluster were previously linked to autoimmunity and SLE, but data are scarce for their association with RA. In the present study, we evaluated associations of five SNPs (rs665691, rs682658, rs172378, rs292001 and rs294179) in the C1q genetic region with RA and some of its clinical and immunologic characteristics. Fifty-eight RA patients and 67 age- and gender-matched healthy controls, all Caucasian, participated in the study. They were genotyped for the five SNPs using TaqMan allelic discrimination assay, and their C1q levels were estimated by ELISA. Rheumatoid factor and anti-citrullinated peptide antibodies were measured (using latex agglutination and ELISA resp.) in the RA patients' group and relevant clinical information was collected. RA patients and healthy controls had similar frequencies of alleles and genotypes of rs665691, rs682658 and rs294179. Minor G-allele and GG genotype of rs172378 were associated with RA (OR = 2.80; 95% CI 1.62-4.81; p = 0.0002 and OR = 5.01; 95% CI 1.55-16.24; p = 0.007, resp.), as well as AA genotype of rs292001 (OR = 3.23; 95% CI 1.15-9.08; p = 0.026). C1q levels were significantly lower (still normal) in RA patients' group compared to healthy volunteers: 89 µg/ml (68-121) vs 114 µg/ml (60-169), p < 0.0001. Significant association was established between rs172378 and rs292001 and RA, in contrast to rs665691, rs682658 and rs294179. RA patients had lower C1q levels than healthy controls. Our findings correspond to the scientific knowledge so far and add additional clarity from a Bulgarian cohort.