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

  • Genes and Disease
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Abstract

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.

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Acknowledgements

We attest that all the authors contributed significantly to the creation of this manuscript, each having fulfilled criteria as established by the ICMJE. We confirm that the manuscript has been read and approved by all named authors. We confirm that the order of authors listed in the manuscript has been approved by all named authors.

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Authors and Affiliations

  1. Department of Propaedeutics of Internal Diseases, Medical University, #1 H. Smirnenski blvd, fl. 13, 9002, Varna, Bulgaria

    Mariya Blagoeva Kosturkova

  2. Clinic of Internal Disease, UMHAT “St. Marina”, Varna, Bulgaria

    Mariya Blagoeva Kosturkova

  3. Department of Biochemistry, Molecular Medicine and Nutrigenomics, Medical University, Varna, Bulgaria

    Galya Mihaylova Mihaylova & Maria Atanasova Radanova

  4. Clinic of Rheumatology, UMHAT “St. Marina”, First Department of Internal Medicine, Medical University, Varna, Bulgaria

    Tanya Kirilova Shivacheva

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  1. Mariya Blagoeva Kosturkova
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  4. Maria Atanasova Radanova
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Contributions

MK participated in the design of the work, patients’ recruitment, analysis of the data, and drafting of the manuscript. GM participated in carrying out samples’ preparation and performing the experiments and revised the work for important intellectual content. TS participated in the patients’ recruitment, interpretation of the data and critically revised the work. MR participated in the designing of the work, healthy controls recruitment, analysis of the data, drafting and editing of the manuscript.

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Correspondence to Mariya Blagoeva Kosturkova.

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We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.

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We confirm that any aspect of the work covered in this manuscript that has involved human patients has been conducted with the ethical approval of all relevant bodies and that such approvals are acknowledged within the manuscript.

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IRB approval was obtained with an approval number No. 73/29.03.2018 and each participant signed an informed consent form on enrollment.

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Kosturkova, M.B., Mihaylova, G.M., Shivacheva, T.K. et al. Association of C1q gene cluster variants with rheumatoid arthritis: a pilot study. Rheumatol Int 42, 1073–1083 (2022). https://doi.org/10.1007/s00296-022-05089-1

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