ClinVar

In a study using admixture mapping to locate regions of the genome associated with acute-phase inflammatory markers and soluble receptors, Reich et al. (2007) identified a missense SNP, rs8192284, that was significantly associated with circulating levels of IL6SR (614689). This SNP, an A-to-C transversion that results in an asp358-to-ala (D358A) amino acid substitution, is present in approximately 35% of Europeans and 4% of West Africans and accounted for the admixture peak within a 40-kb segment on chromosome 1q21.3. Galicia et al. (2004), who had identified the association of rs8192284 with IL6SR in Japanese, noted that this SNP occurs at the proteolytic cleavage site of IL6R and that consequently, variability could affect the level of the circulating soluble receptor. Reich et al. (2007) also identified an association between this SNP and IL6 (147620) levels (614752) in both European Americans and African Americans. After correction for covariates, there was a 1.09- to 1.13-fold increase in IL6SR levels with 1 copy of the C allele of rs8192284 and a 1.24- to 1.43-fold increase with 2 copies, and there was a 1.06- to 1.15-fold increase in IL6 levels with 1 copy of the C allele and a 1.22- to 1.43-fold increase with 2 copies. Surveying cell lines from several different ethnic groups showed no evidence of an association of surface IL6R with rs8192284, supporting the hypothesis of Galicia et al. (2004) that the mechanism of action of rs8192284 is to affect cleavage efficiency.