Association between interleukin-6 gene polymorphism and age at onset of rheumatoid arthritis

Genetic polymorphism of the IL-6 gene (-174 G/C, rs1800795) may affect interleukin-6 expression and contribute to the development of age-associated phenotypes of rheumatoid arthritis (RA).

Objective: to study the distribution of IL-6 gene alleles and genotypes in RA patients depending on age at onset (AAO).

Material and methods. The study included 167 patients with RA. Group 1 included patients with RA AAO ≤45 years (median AAO 36 [29; 42] years; n=95); Group 2 included patients with RA AAO ≥60 years (median AAO 66.5 [62; 70] years; n=72). DNA from 301 healthy donors served as controls. All patients underwent genotyping of IL-6 gene polymorphisms using polymerase chain reaction.

Results and discussion. In patients with AAO ≥60 years, the CC genotype was detected more often than in patients with AAO ≤45 years (31.9% vs 12.6%, respectively; p=0.01). In RA patients with the CC genotype, the risk of developing the disease at the age of ≥60 years was almost three times higher compared with carriers of other genotypes (odds ratio 3.25; 95% confidence interval 1.39–7.65; p=0.004).

Conclusion. The established association of the CC genotype of the -174 G/C polymorphism of the IL-6 gene with the development of RA after 60 years allows this genetic variant to be considered a predictor of RA onset in older age, which supports the rationale for stratifying RA by agerelated phenotypes and opens prospects for the development of diagnostic and preventive approaches.

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