title: The MTHFR C677T mutation is not a risk factor recognized for HBV-related HCC in a population with a high prevalence of this genetic marker.
abstract: Polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene can affect disease progression in HBV infection. However, the results from different reports are inconsistent. The aim of this study was to investigate the association between the MTHFR C677T polymorphism and the outcome of HBV infection in a Tianjin Han population.
  
  
  
  TaqMan SNP genotyping was employed to determine the alleles and genotypes of MTHFR C677T in 2511 subjects from various stages of HBV infection and 549 healthy controls.
  
  
  
  Of the 3060 subjects, the genotypic frequencies were CT 48.9%, TT 29.3% and CC 21.8%; the allelic frequencies were T 53.8% and C 46.2%. There was no significant difference in genotypic or allelic distribution among the different disease groups. When either healthy subjects or self-limited subjects were used as controls, the TT genotype and the T allele conferred protective effects against hepatocellular carcinoma (HCC) (HCC vs healthy subjects: OR=0.588, 95% CI=0.413-0.836, P=0.003; OR=0.768, 95% CI=0.645-0.915, P=0.003, respectively. HCC vs self-limited subjects: OR=0.598, 95% CI=0.404-0.886, P=0.010; OR=0.772, 95% CI=0.635-0.940, P=0.010, respectively). After sub-stratification by gender, the prevalence of the TT genotype or T allele was the lowest in the male HCC group (TT 23.5%, T 49.8%). The protective effects of the TT genotype and the T allele were observed in male HCC and cirrhotic subjects (HCC vs self-limited subjects: OR=0.470, 95% CI=0.288-0.766, P=0.002; OR=0.681, 95% CI=0.535-0.866, P=0.002, respectively. Liver cirrhosis vs self-limited subjects: OR=0.624, 95% CI=0.392-0.992, P=0.046; OR=0.791, 95% CI=0.627-0.998, P=0.048, respectively), but not in female. When the subjects were stratified according to the clinical features, no statistically significant difference in the genotypic distribution was observed (P>0.05).
  
  
  
  The TT genotype and T allele of MTHFR C677T may confer a protective effect on disease progression to HCC in HBV-infected individuals, especially among male patients, in a population with a high prevalence of this genetic marker.
authors.affiliation: Tianjin Key Laboratory of Artificial Cells, Institute for Hepatobiliary Disease, Tianjin Third Central Hospital, Tianjin 300170, China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Jiao
authors.affiliation: Tianjin Key Laboratory of Artificial Cells, Institute for Hepatobiliary Disease, Tianjin Third Central Hospital, Tianjin 300170, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Tianjin Key Laboratory of Artificial Cells, Institute for Hepatobiliary Disease, Tianjin Third Central Hospital, Tianjin 300170, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.affiliation: Tianjin Key Laboratory of Artificial Cells, Institute for Hepatobiliary Disease, Tianjin Third Central Hospital, Tianjin 300170, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jing
authors.affiliation: Tianjin Key Laboratory of Artificial Cells, Institute for Hepatobiliary Disease, Tianjin Third Central Hospital, Tianjin 300170, China.
authors.forename: Yayue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Tianjin Key Laboratory of Artificial Cells, Institute for Hepatobiliary Disease, Tianjin Third Central Hospital, Tianjin 300170, China.
authors.forename: Changzheng
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Ultrasound, Tianjin Third Central Hospital, Tianjin 300170, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Jing
authors.affiliation: Department of Hepatology, Tianjin Third Central Hospital, Tianjin 300170, China.
authors.forename: Fengmei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary Surgery, Tianjin Third Central Hospital, Tianjin 300170, China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory of Artificial Cells, Institute for Hepatobiliary Disease, Tianjin Third Central Hospital, Tianjin 300170, China; Department of Hepatobiliary Surgery, Tianjin Third Central Hospital, Tianjin 300170, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Du
authors.affiliation: Tianjin Key Laboratory of Artificial Cells, Institute for Hepatobiliary Disease, Tianjin Third Central Hospital, Tianjin 300170, China. Electronic address: gaoyt816@163.com.
authors.forename: Yingtang
authors.initials: Y
authors.lastname: Gao
mesh_terms: D000328:Adult; D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics* / Q000473:pathology / Q000821:virology; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D005819:Genetic Markers; D005838:Genotype; D006509:Hepatitis B / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000821:virology; D006515:Hepatitis B virus / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D065840:Protective Factors; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D005819:Genetic Markers; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: Disease progression; Hepatitis B virus; Hepatocellular carcinoma; MTHFR; Polymorphism