A Strong Association of rs1800796 of IL6 and rs4845617 of IL6R In Korean Patients With Dry Eye Disease

Abstract

Purpose: : To determine whether polymorphisms altering the function or expression of proinflammatory cytokine genes, particularly IL6 and IL6R, contribute to the pathogenesis of dry eye disease.

Methods: : Genomic DNA was extracted from blood samples of unrelated dry eye disease patients (non-Sjogren’s syndrome patients (n=521) and Sjogren’s syndrome patients (n=166). Polymerase chain reaction - restriction fragment length polymorphism and direct sequencing were used to screen variations in promoter region, 5 untranslated region and exons of IL6 and IL6R genes. One hundred fifty control individuals without corneal disease were selected from the general population.

Results: : We investigated 8 SNPs for IL6 and 5 SNPs of IL6R; rs1800797 (-597 a>g), rs1800796 (-572 c>g), rs56108454 (A8T12), -353 tins, rs1800795 (-174 g>c) in promoter and rs34280821 (S15L), rs142759801 (P31T) and rs2069830 (P32S) in exon 2 of IL6, and -100 c>t, -93 g>t and -30 a>t in promoter, rs4845617 (EX1 +230 g>a) in 5’ untranslated region and rs2228145 (D358A) in exon 6 of IL6R. Among them, rs1800796 and rs56108454 of IL6 and rs4845617 and rs2228145 of IL6R were significantly different between patients and control groups. In particulary, *c/*c genotype of the rs1800796 (-572 c>g) of IL6 in non-Sjogrens’ and Sjogrens’ patients were significantly increased compared with control subjects (vs. non-Sjogrens’ O.R. =1.667; vs. Sjogrens’ O.R. = 2.571). Also *G/*G genotype of the rs4845617 of IL6R in both dry patient groups were significantly increased compared with control subjects (vs. non-Sjogrens’ O.R. =1.704; vs. Sjogrens’ O.R. = 1.769). The genotype frequencies of rs56108454 of IL6 and rs2228145 of IL6R were showed difference between Sjogrens’ patients and control groups (O.R. = 0.578 and O.R. = 1.119, respectively). The genotype distributions of all polymorphisms of IL6 and IL6R among the control subjects and the affected individuals were in Hardy-Weinberg equilibrium.

Conclusions: : The present study showed that the genetic variants in IL6 and IL6R, in the rs1800796 (-572 c>g) of IL6 and rs4845617 (EX1 +230 g>a) of IL6R, are associated with a higher risk of dry eye disease patients. It is suggested that genetic variations of IL6 and IL6R may act as a potential susceptibility variants in Korean non-Sjogren and Sjogren DED.

Keywords: gene screening • candidate gene analysis