Race-specific association of an IRGM risk allele with cytokine expression in human subjects.
Race-specific association of an IRGM risk allele with cytokine expression in human subjects.
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DOI：
10.1038/s41598-023-40313-3
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发表时间：
2023-08-09
影响因子：
4.6
通讯作者：
Fessler, Michael B. B.
中科院分区：
文献类型：
--
作者：
Ajayi, Teminioluwa;Rai, Prashant;Shi, Min;Gabor, Kristin A. A.;Karmaus, Peer W. F.;Meacham, Julie M. M.;Katen, Kevin;Madenspacher, Jennifer H. H.;Schurman, Shepherd H. H.;Fessler, Michael B. B.
免疫相关GTPase家族M(IRGM)位于人类染色体5q33.1上，编码一种促进自噬和抑制先天免疫反应的蛋白质。Rs13361189(−4299T>；C)的次要等位基因是IRGM启动子上的单核苷酸多态，与包括克罗恩病和肺结核在内的多种疾病有关。尽管这种多态的连锁不平衡模式和次要等位基因频率在欧洲人和非洲人后裔之间有很大差异，但rs13361189的研究主要是在欧洲人进行的，其关联机制尚不清楚。我们招募了68名个体(30名白人，34名非裔美国人，4名其他种族)，他们具有不同的rs13361189基因型别，并评估了一系列免疫反应措施，包括在体外用Toll样受体配体刺激后全血细胞因子的诱导。少数等位基因携带者血清免疫球蛋白M、C反应蛋白和循环CD8+T细胞增加。在整个研究人群中，小等位基因携带者和非等位基因携带者之间的全血细胞因子没有差异；然而，小等位基因状态与非裔美国人受试者中细胞因子亚集的诱导增加有关，而在白人受试者中诱导的细胞因子亚集的诱导减少。这些发现强调了广泛的种族纳入在免疫遗传研究中的重要性。
Immunity-related GTPase family M (IRGM), located on human chromosome 5q33.1, encodes a protein that promotes autophagy and suppresses the innate immune response. The minor allele of rs13361189 (−4299T>C), a single nucleotide polymorphism in the IRGM promoter, has been associated with several diseases, including Crohn’s disease and tuberculosis. Although patterns of linkage disequilibrium and minor allele frequency for this polymorphism differ dramatically between subjects of European and African descent, studies of rs13361189 have predominantly been conducted in Europeans and the mechanism of association is poorly understood. We recruited a cohort of 68 individuals (30 White, 34 African American, 4 other race) with varying rs13361189 genotypes and assessed a panel of immune response measures including whole blood cytokine induction following ex vivo stimulation with Toll-like Receptor ligands. Minor allele carriers were found to have increased serum immunoglobulin M, C-reactive protein, and circulating CD8+ T cells. No differences in whole blood cytokines were observed between minor allele carriers and non-carriers in the overall study population; however, minor allele status was associated with increased induction of a subset of cytokines among African American subjects, and decreased induction among White subjects. These findings underline the importance of broad racial inclusion in genetic studies of immunity.
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影响因子：
3.3
作者：
Meagher, S
通讯作者：
Meagher, S
影响因子：
30.8
作者：
Fisher, Sheila A.;Tremelling, Mark;Anderson, Carl A.;Gwilliam, Rhian;Bumpstead, Suzannah;Prescott, Natalie J.;Nimmo, Elaine R.;Massey, Dunecan;Berzuini, Carlo;Johnson, Christopher;Barrett, Jeffrey C.;Cummings, Fraser R.;Drummond, Hazel;Lees, Charlie W.;Onnie, Clive M.;Hanson, Catherine E.;Blaszczyk, Katarzyna;Inouye, Mike;Ewels, Philip;Ravindrarajah, Radhi;Keniry, Andrew;Hunt, Sarah;Carter, Martyn;Watkins, Nick;Ouwehand, Willem;Lewis, Cathryn M.;Cardon, Lon;Lobo, Alan;Forbes, Alastair;Sanderson, Jeremy;Jewell, Derek P.;Mansfield, John C.;Deloukas, Panos;Mathew, Christopher G.;Parkes, Miles;Satsangi, Jack
通讯作者：
Satsangi, Jack
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作者：
Ness, RB;Haggerty, CL;Ferrell, R
通讯作者：
Ferrell, R
影响因子：
14.2
作者：
Eder, W;Klimecki, W;Martinez, FD
通讯作者：
Martinez, FD
影响因子：
0.4
作者：
Li, Y.;Feng, S. -T.;You, J. -H.
通讯作者：
You, J. -H.