rs8192284

Case-control study of 292 Colombian subjects (191 dengue cases, 101 controls) evaluating associations between dengue susceptibility and polymorphisms in IL6R (rs8192284), TLR3 (rs3775290), and DC-SIGN (rs7248637). In Afro-Colombians, the C allele of rs8192284 was protective (OR=0.425, p=0.020), while the A alleles of rs7248637 and rs3775290 increased risk (OR=2.389, p=0.015 and OR=2.329, p=0.005 in Mestizos). The CAG allelic combination remained significantly associated with dengue after Amerindian ancestry adjustment (OR=2.16, p=0.028).

This study examined 39 RA patients and found that the rs8192284 (A>C) polymorphism in IL6R significantly influences plasma soluble IL-6 receptor levels, with CC carriers showing higher levels (52.55 ng/ml) compared to AC (45.50 ng/ml) and AA (35.27 ng/ml) genotypes (P=0.0001). The association between sIL-6R levels and disease activity (DAS28) was dependent on anti-CCP antibody status: positive correlation in anti-CCP-positive patients (r²=0.45, P=0.034) but negative trend in anti-CCP-negative patients (r²=-0.45, P=0.083).

Genome-wide association study identified five genetic loci influencing C-reactive protein (CRP) levels: rs6700896 in LEPR (-14.7% per allele, OR 1.06 for CHD), rs4537545 in IL6R (-10.8%, OR 0.94 for CHD), rs7553007 in CRP locus (-20.7%, OR 0.98 for CHD), rs1183910 in HNF1A (-13.6%), and rs4420638 in APOE-CI-CII (-21.8%, OR 1.16 for CHD). Mendelian randomization analysis of 28,112 CHD cases and 100,823 controls found no causal association between CRP genetic variants and coronary heart disease (OR 1.00, 95% CI 0.97-1.02), arguing against CRP having a causal role in atherosclerosis.

A meta-analysis of 4,107 type 2 diabetes cases and 5,187 controls from three GWA studies found no evidence that common variants altering circulating inflammatory protein levels (IL-18, IL-6R, CRP, IL1RN, PAI1, MIF) or variants predisposing to autoimmune diseases (type 1 diabetes, rheumatoid arthritis, Crohn's disease, celiac disease, multiple sclerosis, SLE) are associated with type 2 diabetes risk. For example, rs2250417 in IL18 showed OR=1.00 (95% CI 0.99-1.03) versus the expected OR of ~1.15 if inflammation were causal, suggesting inflammatory markers are likely secondary rather than causative in type 2 diabetes.

This journal issue contains multiple genetic association studies on rheumatoid arthritis (RA). A key REMARCA study (146 aCCP+ RA patients vs 314 controls) identified polymorphisms in CTLA4 (rs231775 +49A/G), IL10 (rs1800872 -592A/C), and IL6R (rs8192284 +358A/C) associated with high inflammatory disease activity, with CTLA4 and IL10 minor alleles showing increased risk (OR=1.4, p=0.02 and OR=1.9, p<0.0001 respectively) and IL6R minor allele being protective (OR=0.7, p=0.03). A separate study analyzed NOS3, PPARG, PPARGC1A, PPARGC1B and PAI1 polymorphisms in 73 RA patients for cardiovascular risk.

Candidate gene association study of 122 early rheumatoid arthritis (RA) patients and 314 healthy controls found that PTPN22 rs2476601 (OR=1.5, 95% CI 1.0-2.3, p=0.05) and TNFAIP3 rs675520 (OR=1.7) polymorphisms were significantly associated with RA risk. Anti-cyclic citrullinated peptide (ACPA) antibody production was associated with PTPN22, TNFAIP3, CTLA4, and TNF-α polymorphisms in a dose-dependent manner.