Interleukin 12B (IL12B) genetic variation and pulmonary tuberculosis: a study of cohorts from The Gambia, Guinea-Bissau, United States and Argentina.
Interleukin 12B (IL12B) genetic variation and pulmonary tuberculosis: a study of cohorts from The Gambia, Guinea-Bissau, United States and Argentina.
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DOI：
10.1371/journal.pone.0016656
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发表时间：
2011-02-09
期刊：
影响因子：
3.7
通讯作者：
Sirugo G
中科院分区：
文献类型：
--
作者：
Morris GA;Edwards DR;Hill PC;Wejse C;Bisseye C;Olesen R;Edwards TL;Gilbert JR;Myers JL;Stryjewski ME;Abbate E;Estevan R;Hamilton CD;Tacconelli A;Novelli G;Brunetti E;Aaby P;Sodemann M;Østergaard L;Adegbola R;Williams SM;Scott WK;Sirugo G
我们在两个西非人群（来自冈比亚和几内亚比绍）和两个来自北美和南美的独立人群中研究了白细胞介素-12 B（IL 12 B）多态性是否与肺结核（PTB）易感性相关。在几内亚比绍的321例PTB病例和346例对照以及冈比亚的280例PTB病例和286例对照中分析了9种多态性（7种SNP，1种插入/缺失，1种微卫星）。为了重复，我们研究了281例和179个对照的非洲裔美国人样本和221例和144个来自美国和阿根廷的欧洲血统的对照。第一阶段单基因座分析显示，几内亚比绍的IL 12 B 3′ UTR SNP rs3212227（未校正等位基因p = 0.04;加性基因型p = 0.05，OR = 0.78，95%CI [0.61-0.99]）和冈比亚的rs 11574790（未校正等位基因p = 0.05;加性基因型p = 0.05，OR = 0.76，95%CI [0.58-1.00]）存在关联信号。 rs3212227的关联随后在非裔美国人中复制（rs3212227等位基因p = 0.002;加性基因型p = 0.05，OR = 0.78，95%CI [0.61-1.00]）;最重要的是，在非裔美国人队列中，在整个基因中检测到多个显著的关联信号（检测的9个多态性中的7个）。 这些数据表明，IL 12 B（一种高度相关的候选基因）的遗传变异是非洲血统人群中PTB的一个风险因素，尽管需要进一步的研究来证实这种关联并确定其背后的确切机制。
We examined whether polymorphisms in interleukin-12B (IL12B) associate with susceptibility to pulmonary tuberculosis (PTB) in two West African populations (from The Gambia and Guinea-Bissau) and in two independent populations from North and South America. Nine polymorphisms (seven SNPs, one insertion/deletion, one microsatellite) were analyzed in 321 PTB cases and 346 controls from Guinea-Bissau and 280 PTB cases and 286 controls from The Gambia. For replication we studied 281 case and 179 control African-American samples and 221 cases and 144 controls of European ancestry from the US and Argentina. First-stage single locus analyses revealed signals of association at IL12B 3′ UTR SNP rs3212227 (unadjusted allelic p = 0.04; additive genotypic p = 0.05, OR = 0.78, 95% CI [0.61–0.99]) in Guinea-Bissau and rs11574790 (unadjusted allelic p = 0.05; additive genotypic p = 0.05, OR = 0.76, 95% CI [0.58–1.00]) in The Gambia. Association of rs3212227 was then replicated in African-Americans (rs3212227 allelic p = 0.002; additive genotypic p = 0.05, OR = 0.78, 95% CI [0.61–1.00]); most importantly, in the African-American cohort, multiple significant signals of association (seven of the nine polymorphisms tested) were detected throughout the gene. These data suggest that genetic variation in IL12B, a highly relevant candidate gene, is a risk factor for PTB in populations of African ancestry, although further studies will be required to confirm this association and identify the precise mechanism underlying it.
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DOI：
10.1084/jem.20050126
发表时间：
2005-12-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Flores-Villanueva PO;Ruiz-Morales JA;Song CH;Flores LM;Jo EK;Montaño M;Barnes PF;Selman M;Granados J
通讯作者：
Granados J
影响因子：
4.4
作者：
DEVLIN, B;RISCH, N
通讯作者：
RISCH, N
DOI：
10.1164/rccm.200601-088oc
发表时间：
2006-08-01
影响因子：
24.7
作者：
Cooke, Graham S.;Campbell, Sarah J.;Hill, Adrian V. S.
通讯作者：
Hill, Adrian V. S.
影响因子：
56.9
作者：
Gabriel, SB;Schaffner, SF;Altshuler, D
通讯作者：
Altshuler, D
影响因子：
9.8
作者：
Martin, ER;Bass, MP;Kaplan, NL
通讯作者：
Kaplan, NL