CD81 and CLDN1 polymorphisms and hepatitis C virus infection susceptibility: a case control study.
CD81 and CLDN1 interact to form a CD81-CLDN1 co-receptor complex that is crucial in hepatitis C virus (HCV) entry. Variations in the two genes were shown to influence immunological functions; therefore, we hypothesized that polymorphisms in these genes may contribute to HCV susceptibility. A case-control study consisting of 461 patients and 461 controls was conducted to explore the associations between CD81 rs708564 and CLDN1 rs893051 and HCV susceptibility in a Chinese population. We found a decreased HCV risk associated with the CD81 rs708564 TT (odds ratio (OR) = 0.66, 95% CI = 0.44-0.98) genotype. The gene-gene interaction between CD81 and CLDN1 polymorphisms also decreased HCV risk in a joint multiplicative manner (OR for the presence of both CD81 rs708564 TT and CLDN1 rs893051 GG genotypes = 0.59, 95% CI = 0.36-0.97). Furthermore, the CD81 rs708564 TT genotype conferred a more pronounced decrease in HCV susceptibility in combination with lower levels of high-density lipoprotein cholesterol (HDL-C; OR = 0.71, 95% CI = 0.52-0.96), and higher levels of low-density lipoprotein cholesterol (OR = 0.24, 95% CI = 0.09-0.65). We also observed a decreased HCV susceptibility in individuals with higher HDL-C levels who carried the CLDN1 rs893051 G/C genotype. These findings suggest that homozygous CD81 rs708564 TT may be a genetic modifier for avoiding HCV infection whether as a sole single nucleotide polymorphism or combined with the CLDN1 rs893051 GG genotype, and this effect is associated with serum levels of lipoprotein.
Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.
Shuang
S
Sun
Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.
Guojiang
G
Jin
Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China. Electronic address: cmukanghui@163.com.
Hui
H
Kang
D001483:Base Sequence; D016022:Case-Control Studies; D062445:Claudin-1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006526:Hepatitis C / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D060225:Tetraspanin 28 / Q000235:genetics*
C554798:CD81 protein, human; C568108:CLDN1 protein, human; D062445:Claudin-1; D060225:Tetraspanin 28
CD81; CLDN1; Hepatitis C virus; Polymorphism