title: Vitamin D level and vitamin D receptor genetic variations contribute to HCV infection susceptibility and chronicity in a Chinese population.
abstract: Vitamin D and vitamin D receptor (VDR) are involved in multiple immune-mediated disorders including chronic hepatitis C virus (HCV) infection. The aim of this study was to determine the association between plasma vitamin D level, VDR genetic polymorphisms and risk of HCV infection susceptibility and chronicity. Seven single nucleotide polymorphisms (SNPs) in VDR gene were genotyped and plasma 25-hydroxyvitamin D [25(OH)D] levels were measured in a Han Chinese population of 898 HCV persistent infection cases, 558 spontaneous clearance subjects and 1136 uninfected controls with high risk of HCV infection. In this case-control study, the average plasma 25(OH)D level in persistent infection patients was significantly lower than that in spontaneous clearance cases (P=0.039) and controls (P=0.005). Logistic analyses indicated that rs7975232-C, rs2239185-T and rs11574129-T alleles were significantly associated with a decreased risk of HCV infection susceptibility (all PBonferroni<0.05, in additive/dominant models; Ptrend=9.000×10(-4), combined effects in a locus-dosage manner). The protective effects of three favorable alleles were more evident among males, females and subjects aged ≤50years (all P<0.05). Haplotype analyses suggested that compared with the most frequent haplotype Ars7975232Trs731236Crs11574129, CTT was correlated with a reduced risk of HCV infection susceptibility (P=2.200×10(-3)). These findings implied that low vitamin D levels might be associated with an increased risk for HCV infection and chronicity, and favorable VDR variants (rs7975232-C, rs2239185-T and rs11574129-T) might contribute to a decreased susceptibility to HCV infection in a high-risk Chinese population.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, No. 818 East Tianyuan Road, Nanjing 211166, Jiangsu, China.
authors.forename: Mengping
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, 210029, Nanjing, Jiangsu, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yue
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, No. 818 East Tianyuan Road, Nanjing 211166, Jiangsu, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.affiliation: Huadong Research Institute for Medicine and Biotechnics, No. 293 Zhongshan East Road, Nanjing 210002, Jiangsu, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, No. 818 East Tianyuan Road, Nanjing 211166, Jiangsu, China.
authors.forename: Chaonan
authors.initials: C
authors.lastname: Xie
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, No. 818 East Tianyuan Road, Nanjing 211166, Jiangsu, China.
authors.forename: Rongbin
authors.initials: R
authors.lastname: Yu
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, 210029, Nanjing, Jiangsu, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Basic and Community Nursing, School of Nursing, Nanjing Medical University, No. 818 East Tianyuan Road, Nanjing 211166, Jiangsu, China. Electronic address: wangjienjmu@126.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000483:Alleles; D044466:Asian People; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D016174:Hepacivirus / Q000254:growth & development* / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000097:blood / Q000208:ethnology / Q000235:genetics* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000097:blood / Q000235:genetics*; D012075:Remission, Spontaneous; D012306:Risk; D012720:Severity of Illness Index; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D018167:Receptors, Calcitriol; C579457:VDR protein, human; D014807:Vitamin D; C104450:25-hydroxyvitamin D
keywords: Hepatitis C virus; Polymorphism; Vitamin D; Vitamin D receptor