Genome-wide association study identifies variants associated with progression of liver fibrosis from HCV infection.
Genome-wide association study identifies variants associated with progression of liver fibrosis from HCV infection.
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全基因组关联研究确定了与HCV感染的肝纤维化进展相关的变异。
DOI：
10.1053/j.gastro.2012.07.097
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发表时间：
2012-11
期刊：
影响因子：
29.4
通讯作者：
French ANRS HC EP 26 Genoscan Study Group
中科院分区：
文献类型：
--
作者：
Patin E;Kutalik Z;Guergnon J;Bibert S;Nalpas B;Jouanguy E;Munteanu M;Bousquet L;Argiro L;Halfon P;Boland A;Müllhaupt B;Semela D;Dufour JF;Heim MH;Moradpour D;Cerny A;Malinverni R;Hirsch H;Martinetti G;Suppiah V;Stewart G;Booth DR;George J;Casanova JL;Bréchot C;Rice CM;Talal AH;Jacobson IM;Bourlière M;Theodorou I;Poynard T;Negro F;Pol S;Bochud PY;Abel L;Swiss Hepatitis C Cohort Study Group, International Hepatitis C Genetics Consortium;French ANRS HC EP 26 Genoscan Study Group
在全基因组关联(GWA)研究中，IL28B基因的多态被证明影响丙型肝炎病毒(HCV)感染的清除。只有一小部分慢性丙型肝炎患者会出现肝纤维化，这一过程可能也会受到遗传因素的影响。我们进行了一项与丙型肝炎病毒感染相关的肝纤维化进展的两阶段GWA研究。我们研究了特征良好的欧洲血统丙型肝炎病毒感染患者，他们在治疗前进行了肝脏活检。我们根据Metavir评分，在考虑和不考虑丙型肝炎病毒感染持续时间的情况下，定义了不同的肝纤维化表型。我们的GWA分析是使用780,650个单核苷酸多态(SNPs)对1161名患者的筛选后的初级队列进行的。我们从962名患者的独立复制队列中对96个P值为5×10−5的SNPs进行了基因分型。然后，我们使用从219名患者收集的DNA样本来评估最有趣的复制SNPs，这些患者参与了单独的GWA丙型肝炎病毒清除研究。在2342例丙型肝炎合并感染患者中，rs16851720(总样本)和rs4374383(在接受输血的患者中)与肝纤维化进展相关(P合并分别为8.9×10−9和1.1×10−9)。SNP rs16851720位于RNF7内，RNF7编码一种抗氧化剂，可防止细胞凋亡。SNP rs4374383和另一个复制的SNP rs9380516(P组合=5.4×10−7)与功能相关基因MERTK和TULP1连锁，这两个基因编码参与巨噬细胞吞噬凋亡细胞的因子。我们的GWA研究确定了几个丙型肝炎病毒诱导的肝纤维化的易感基因；这些易感基因与调节细胞凋亡的基因有关。因此，细胞凋亡控制可能与肝纤维化有关。
Polymorphisms in IL28B were shown to affect clearance of hepatitis C virus (HCV) infection in genome-wide association (GWA) studies. Only a fraction of patients with chronic HCV infection develop liver fibrosis, a process that might also be affected by genetic factors. We carried out a 2-stage GWA study of liver fibrosis progression related to HCV infection. We studied well-characterized HCV-infected patients of European descent who had liver biopsies before treatment. We defined various liver fibrosis phenotypes on the basis of Metavir scores, with and without taking the duration of HCV infection into account. Our GWA analyses were conducted on a filtered primary cohort of 1161 patients using 780,650 single nucleotide polymorphisms (SNPs). We genotyped 96 SNPs with P-values<5×10−5 from an independent replication cohort of 962 patients. We then assessed the most interesting replicated SNPs using DNA samples collected from 219 patients who participated in separate GWA studies of HCV clearance. In the combined cohort of 2342 HCV-infected patients, the SNPs rs16851720 (in the total sample) and rs4374383 (in patients that received blood transfusions) were associated with fibrosis progression (Pcombined=8.9×10−9 and 1.1×10−9, respectively). The SNP rs16851720 is located within RNF7, which encodes an antioxidant that protects against apoptosis. The SNP rs4374383, together with another replicated SNP, rs9380516 (Pcombined=5.4×10−7), were linked to the functionally related genes MERTK and TULP1, which encode factors involved in phagocytosis of apoptotic cells by macrophages. Our GWA study identified several susceptibility loci for HCV-induced liver fibrosis; these were linked to genes that regulate apoptosis. Apoptotic control might therefore be involved in liver fibrosis.
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影响因子：
30.8
作者：
Banerjee, P;Kleyn, PW;Gilliam, TC
通讯作者：
Gilliam, TC
影响因子：
29.4
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Chalasani N;Guo X;Loomba R;Goodarzi MO;Haritunians T;Kwon S;Cui J;Taylor KD;Wilson L;Cummings OW;Chen YD;Rotter JI;Nonalcoholic Steatohepatitis Clinical Research Network
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Nonalcoholic Steatohepatitis Clinical Research Network
影响因子：
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作者：
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13.5
作者：
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通讯作者：
Poynard, T
影响因子：
29.4
作者：
Huang, Hongjin;Shiffman, Mitchell L.;Wright, Teresa L.
通讯作者：
Wright, Teresa L.