A genome‐wide association study on low susceptibility to hepatitis C virus infection (GEHEP012 study). (10th July 2019)

• Record Type: Journal Article
• Authors: Real, Luis M.; Fernández‐Fuertes, Marta; Sáez, María E.; Rivero‐Juárez, Antonio; Frías, Mario; Téllez, Francisco; Santos, Jesús; Merino, Dolores; Moreno‐Grau, Sonia; Gómez‐Salgado, Juan; González‐Serna, Alejandro; Corma‐Gómez, Anais; Ruiz, Agustín; Macías, Juan; Pineda, Juan A.
• Is Part Of: Liver international. Volume 39:Number 10(2019)
• Page Start: 1918
• Page End: 1926
• Publication Date: 2019-07-10
• Subjects: exposed uninfected -- genetics -- GWAS -- hepatitis C virus -- high‐risk HCV seronegative -- resistance -- susceptibility; Liver -- Periodicals; Liver -- Diseases -- Periodicals; 616.362
• DOI: 10.1111/liv.14177
• Languages: English
• ISSNs: 1478-3223

Abstract

Abstract: Background: A low proportion of individuals repeatedly exposed to the hepatitis C virus (HCV) remain uninfected. This condition could have a genetic basis but it is not known whether or not it is mainly driven by a high‐penetrance common allele. Objective: To explore whether low susceptibility to HCV infection is mainly driven by a high‐penetrance common allele. Methods: In this genome‐wide association study (GWAS), a total of 804 HCV‐seropositive individuals and 27 high‐risk HCV‐seronegative (HRSN) subjects were included. Plink and Magma software were used to carry out single nucleotide polymorphism (SNP)‐based and gene‐based association analyses respectively. Results: No SNP nor any gene was associated with low susceptibility to HCV infection after multiple testing correction. However, SNPs previously associated with this trait and allocated within the LDLR gene, rs5925 and rs688, were also associated with this condition in our study under a dominant model (24 out of 27 [88.9%] rs5925‐C carriers in the HRSN group vs 560 of 804 [69.6%] rs5925‐C carriers in the HCV‐seropositive group, P = 0.031, odds ratio [OR] = 3.48; 95% confidence interval [CI] = 1.04‐11.58; and 24 out of 27 [88.9%] rs688‐T carriers in the HRSN group vs 556 of 804 [69.1%] rs688‐T carriers in the HCV‐seropositive group, P = 0.028, OR = 3.57, 95% CI = 1.65‐11.96). Conclusions: Low susceptibility to HCV infection does not seem to be mainly driven by a high‐penetrant common allele. By contrast, it seems a multifactorial trait where genes such as LDLR could be involved.