rs4129267

A 2012 educational article explained that in autoimmune inflammatory conditions, IL-6 promotes antibody production, drives CRP levels, and has other pathological roles. A 2013 article titled "Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci" stated that the OR for the risk allele was 1.14 (1.18 in Caucasians, but only 0.99 in Asians), but the TT polymorphism was more significant. TT homozygous at rs4129267 had sIL-6R (soluble inhibiting IL-6 receptors) concentrations 73% higher than CC homozygous (28.9 versus 16.7 ng/ml; P = 7.8 × 10−17) and CRP (C-reactive protein) concentrations were 30% higher in TT than in CC (19.2 versus 14.8 mg/l). A 2008 article. Soluble IL6R (sIL-6R) protein levels A 2008 study titled "Loci related to metabolic-syndrome pathways including LEPR,HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the Women's Genome Health Study" explained that "elevated levels of C-reactive protein (CRP) independently predict increased risk of development of metabolic syndrome, diabetes, myocardial infarction, and stroke" (Abstract). The IL6R SNP rs4129267 had an influence on median hsCRP levels (mg/l). They were 1.65 for Minor allele homozygous, 1.95 for heterozygous, and 1.98 for major allele homozygous. A 2008 article titled "Polymorphisms of the HNF1A gene encoding hepatocyte nuclear factor-1 alpha are associated with C-reactive protein" reported "results of two genetic-association studies of CRP, the Pharmacogenomics and Risk of Cardiovascular Disease (PARC) study and the Cardiovascular Health Study (CHS)." They were unable to find association between this SNP and CRP levels, but said this lack of finding may be due to their smaller sample size. "Interleukin-6 receptor gene, plasma C-reactive protein, and diabetes risk in women." This 2009 article explained that "SNP rs4129267 reported by the GWAS (9) was not typed in the present study. However, this SNP is in near perfect linkage disequilibrium with rs8192284 (D′ = 1 and r2 = 0.96; HapMap, CEU)." The latter SNP genotype rs8192284 AA (major allele) carried a higher risk of type 2 diabetes (OD =1 in the lowest quartile of the sample, OR=5 in the highest quartile). ORs for AC+CC (C is the minor allele) ranged from 1 to 3. . Published 2011. In the analysis of 15,797 asthmatic patients and 42,003 controls, researchers found rs4129267 SNP's minor allele a risk for Asthma (OR 1·09, combined p=2·4×10(-8)) . Published 2012. Stated "The SNP rs4129267 is in linkage disequilibrium (r(2) = 1) with the IL6R coding SNP rs2228145 (Asp(358)Ala). This IL6R coding change increases IL-6 receptor (IL-6R) shedding and promotes IL-6 transsignaling." (Abstract) Genome-wide association analysis of metabolic traits in a birth cohort from a founder population. Genome-wide association studies in an isolated founder population from the Pacific Island of Kosrae. Parasites represent a major selective force for interleukin genes and shape the genetic predisposition to autoimmune conditions. "Multiple Novel loci, including those related to Crohn disease, psoriasis, and inflammation, identified in a genome-wide association study of fibrinogen in 17 686 women: the Women's Genome Health Study." This 2009 study noted a strong association with this SNP but provided no risk alleles or odds ratios. A 2011 study of 302 Breast cancer survivors, and follow-up data from 236 of them, "Fatigued breast cancer survivors and gene polymorphisms in the inflammatory pathway" examined "The associations between fatigue and SNPs in inflammation-related genes; IL1β (rs16944), IL6 (rs1800795), IL6receptor (rs4129267, rs4845617, rs2228145), CRP (rs2794521, rs3091244)" (Abstract). They found borderline significance associated with rs3091244, but no others. They suggested that they could not replicate the finding of CRP levels in association with (rs2228145 and rs4129267) due to their small sample size. Genome-wide association with C-reactive protein levels in CLHNS: evidence for the CRP and HNF1A loci and their interaction with exposure to a pathogenic environment. A 2007 article "Genome-wide association to body mass index and waist circumference: the Framingham Heart Study 100K project" listed this SNP among supplementary data on a separate website, but did not provide any discussion of the SNP in text.

T;T

A 2012 educational article explained that in autoimmune inflammatory conditions, IL-6 promotes antibody production, drives CRP levels, and has other pathological roles. A 2013 article titled "Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci" stated that TT homozygous at rs4129267 had sIL-6R (soluble inhibiting IL-6 receptors) concentrations 73% higher than CC homozygous (28.9 versus 16.7 ng/ml; P = 7.8 × 10−17) and CRP (C-reactive protein) concentrations were 30% higher in TT than in CC (19.2 versus 14.8 mg/l). See further references at rs4129267