Polymorphism in IL1B-ILIB-511 association with tuberculosis and decreased lipopolysaccharide-induced IL-1β in IFN-γ primed ex-vivo whole blood assay

Polymorphism in IL1B-ILIB-511 association with tuberculosis and decreased lipopolysaccharide-induced IL-1β in IFN-γ primed ex-vivo whole blood assay
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DOI:
10.1179/096805105x58706
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发表时间:
2005-01-01
期刊:
JOURNAL OF ENDOTOXIN RESEARCH
影响因子:
--
通讯作者:
Newport, MJ
Newport, MJ
中科院分区:
其他
文献类型:
--
作者:
Awomoyi, AA;Charurat, M;Newport, MJ

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为了确定白细胞介素1家族基因(IL 1B和IL 1 RN)的变异是否与肺结核(TB)相关,对335例涂片阳性冈比亚TB患者和298例种族匹配的对照者进行了IL 1B-511和+3953核苷酸位点多态性和IL 1 RN 86 bp VNTR多态性的基因分型。所有人都是艾滋病毒阴性。肺结核风险的降低与IL 1B-511-C等位基因的杂合性和纯合性相关(OR分别为0.66,P = 0.027和0.58,P = 0.015)。尽管如此,C等位基因在TB病例中以0.66的频率存在,这表明虽然IL-1 β有助于疾病易感性,但它不是主要因素。在该人群中,IL 1B +3953-T/C多态性或86 bp IL 1 RN五等位基因重复与TI 3之间没有关联。使用离体全血测定,IL 1B-511-T等位基因纯合的健康冈比亚个体在IFN-γ引发后响应于LPS未能表现出IL-1 β产生的显著增加。
To determine whether variation in two interleukin 1 family genes (IL1B and interleukin 1 receptor antagonist, IL1RN) is associated with pulmonary tuberculosis (TB), two published polymorphisms at nucleotide positions -511 and +3953 in IL1B and one in the IL1RN 86 bp VNTR were genotyped in 335 smear positive Gambian TB patients, and 298 ethnically matched controls. All individuals were HIV negative. Decreased risk of pulmonary TB was associated with both heterozygosity and homozygosity for the IL1B-511-C allele (OR 0.66, P = 0.027, and OR 0.58, P = 0.015, respectively). Nonetheless, the C allele was present at a frequency of 0.66 in TB cases suggesting that whilst IL-1 beta contributes to disease susceptibility, it is not the major factor. There was no association between the IL1B+3953-T/C polymorphism or the 86 bp IL1RN pentallelic repeat and TI3 in this population. Using an ex-vivo whole blood assay, healthy Gambian individuals who are homozygous for the IL1B-511-T allele failed to exhibit a significant increase in IL-1 beta production in response to LPS after IFN-gamma priming.