Interleukin-6 (IL-6) is a key inflammatory cytokine, signalling to most tissues by binding to a soluble IL-6 receptor (sIL-6r), making a complex with gp130. We used 1273 subjects (mean age 68 years) from the InCHIANTI Italian cohort to study common variation in the IL-6r locus and associations with interleukin 6 receptor (IL-6r), IL-6, gp130 and a battery of inflammatory markers. The rs4537545 single nucleotide polymorphism (SNP) tags the functional non-synonymous Asp358Ala variant (rs8192284) in IL-6r (r(2)=0.89, n=343). Individuals homozygous for the rs4537545 SNP minor allele (frequency 40%) had a doubling of IL-6r levels (132.48 pg/ml, 95% CI 125.13-140.27) compared to the common allele homozygous group (68.31 pg/ml, 95% CI 65.35-71.41): in per allele regression models, the rs4537545 SNP accounted for 20% of the variance in sIL-6r, with P=5.1 x 10(-62). The minor allele of rs4537545 was also associated with higher circulating IL-6 levels (P=1.9 x 10(-4)). There was no association of this variant with serum levels of gp130 or with any of the studied pro- and anti-inflammatory markers. A common variant of the IL-6r gene results in major changes in IL-6r and IL-6 serum levels, but with no apparent effect on gp130 levels or on inflammatory status in the general population.

中文翻译：

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白介素6受体（IL-6r）基因的常见变体可增加IL-6r和IL-6水平，而无其他炎症作用。

白细胞介素6（IL-6）是关键的炎症细胞因子，通过与可溶性IL-6受体（sIL-6r）结合而向大多数组织发出信号，从而与gp130形成复合物。我们使用了来自意大利INCHIANTI队列的1273名受试者（平均年龄68岁）来研究IL-6r基因座的常见变异以及与白介素6受体（IL-6r），IL-6，gp130和一系列炎症标志物的关联。rs4537545单核苷酸多态性（SNP）在IL-6r中标记功能非同义的Asp358Ala变体（rs8192284）（r（2）= 0.89，n = 343）。与普通等位基因纯合组（68.31 pg / ml，95％CI）相比，rs4537545 SNP次要等位基因纯合子（频率40％）的IL-6r水平翻了一番（132.48 pg / ml，95％CI 125.13-140.27） 65.35-71.41）：在每个等位基因回归模型中，rs4537545 SNP占sIL-6r方差的20％，P = 5。1 x 10（-62）。rs4537545的次要等位基因也与较高的循环IL-6水平相关（P = 1.9 x 10（-4））。该变体与gp130的血清水平或任何已研究的促炎和抗炎标志物没有关联。IL-6r基因的常见变异导致IL-6r和IL-6血清水平发生重大变化，但对普通人群中gp130水平或炎症状态没有明显影响。