Genome-wide association study of spontaneous resolution of hepatitis C virus infection: data from multiple cohorts.
Genome-wide association study of spontaneous resolution of hepatitis C virus infection: data from multiple cohorts.
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DOI：
10.7326/0003-4819-158-4-201302190-00003
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发表时间：
2013-02-19
影响因子：
39.2
通讯作者：
Thomas DL
中科院分区：
文献类型：
--
作者：
Duggal P;Thio CL;Wojcik GL;Goedert JJ;Mangia A;Latanich R;Kim AY;Lauer GM;Chung RT;Peters MG;Kirk GD;Mehta SH;Cox AL;Khakoo SI;Alric L;Cramp ME;Donfield SM;Edlin BR;Tobler LH;Busch MP;Alexander G;Rosen HR;Gao X;Abdel-Hamid M;Apps R;Carrington M;Thomas DL
Hepatitis C virus (HCV) infections occur worldwide and either spontaneously resolve or persist and markedly increase the person’s lifetime risk of cirrhosis and hepatocellular carcinoma. Although HCV persistence occurs more often in persons of African ancestry and in persons with a genetic variant near IL28B, the genetic basis is not well understood. To evaluate the host genetic basis for spontaneous resolution of HCV infection. Two-stage genome wide association study (GWAS). 13 international multicenter study sites. 919 individuals with serum HCV antibodies but no HCV RNA (spontaneous resolution) and 1482 individuals with serum HCV antibodies and RNA (persistence). Frequencies of 792,721 SNPs. Differences in allele frequencies between persons with spontaneous resolution and persistence were identified on chromosomes 19q13.13 and 6p21.32. On chromosome 19, allele frequency differences localized near IL28B and included rs12979860 (overall per-allele OR = 0.45, P = 2.17 × 10−30) and 10 additional SNPs spanning 55,000 bases. On chromosome 6, allele frequency differences localized near genes for class II human leukocyte antigens (HLA) and included rs4273729 (overall per-allele OR= 0.59, P = 1.71 × 10−16) near DQB1*03:01 and an additional 116 SNPs spanning 1,090,000 base pairs. The associations in chromosomes 19 and 6 were independent, additive, and explain an estimated 14.9% (95% CI: 8.5–22.6%) of the variation in HCV resolution in those of European-Ancestry, and 15.8% (95% CI:4.4–31.0%) in individuals of African-Ancestry. Replication of the chromosome 6 SNP, rs4272729 in an additional 746 individuals confirmed the findings (p=0.015). Epigenetic effects were not studied. IL28B and HLA class II are independently associated with spontaneous resolution of HCV infection and SNPs marking IL28B and DQB1*03:01 may explain ~15% of spontaneous resolution of HCV infection.
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影响因子：
13.5
作者：
Fanning, LJ;Levis, J;Shanahan, F
通讯作者：
Shanahan, F
影响因子：
158.5
作者：
Kenny-Walsh, E
通讯作者：
Kenny-Walsh, E
影响因子：
4.5
作者：
Fellay J;Ge D;Shianna KV;Colombo S;Ledergerber B;Cirulli ET;Urban TJ;Zhang K;Gumbs CE;Smith JP;Castagna A;Cozzi-Lepri A;De Luca A;Easterbrook P;Günthard HF;Mallal S;Mussini C;Dalmau J;Martinez-Picado J;Miro JM;Obel N;Wolinsky SM;Martinson JJ;Detels R;Margolick JB;Jacobson LP;Descombes P;Antonarakis SE;Beckmann JS;O'Brien SJ;Letvin NL;McMichael AJ;Haynes BF;Carrington M;Feng S;Telenti A;Goldstein DB;NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI)
通讯作者：
NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI)
影响因子：
13.5
作者：
Kuniholm, Mark H.;Kovacs, Andrea;Gao, Xiaojiang;Xue, Xiaonan;Marti, Darlene;Thio, Chloe L.;Peters, Marion G.;Terrault, Norah A.;Greenblatt, Ruth M.;Goedert, James J.;Cohen, Mardge H.;Minkoff, Howard;Gange, Stephen J.;Anastos, Kathryn;Fazzari, Melissa;Harris, Tiffany G.;Young, Mary A.;Strickler, Howard D.;Carrington, Mary
通讯作者：
Carrington, Mary
影响因子：
30.8
作者：
Skol, AD;Scott, LJ;Boehnke, M
通讯作者：
Boehnke, M