Study of the Association Between Polymorphisms of the COL1A1 Gene and HBV-Related Liver Cirrhosis in Chinese Patients

被引:13
作者
Zhao, Yun-Peng [1 ]
Wang, Hao [2 ]
Fang, Meng [1 ]
Ji, Qiang [1 ]
Yang, Zai-Xing [2 ]
Gao, Chun-Fang [1 ]
机构
[1] Second Mil Med Univ, Eastern Hepatobiliary Hosp, Dept Lab Med, Shanghai, Peoples R China
[2] Second Mil Med Univ, Changzheng Hosp, Dept Lab Med, Shanghai, Peoples R China
基金
中国国家自然科学基金;
关键词
Cirrhosis; Fibrosis; Collagen; Polymorphism; Promoter; HEPATIC STELLATE CELLS; BONE-MINERAL DENSITY; ALPHA-1(I) PROCOLLAGEN GENE; FINGER TRANSCRIPTION FACTOR; I COLLAGEN GENES; INTERFERON-GAMMA; EXPRESSION; PROMOTER; FIBROSIS; FIBROBLASTS;
D O I
10.1007/s10620-008-0340-9
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
To investigate the association between polymorphisms of the COL1A1 gene and liver cirrhosis. A total of 111 liver cirrhotic patients and 95 matched controls were recruited. Polymorphisms -1997T > G, -1663 ins/del T and -1363C > G of the COL1A1 gene were detected by direct sequencing. The activities of the putative promoters containing these polymorphisms were analyzed by means of the reporter gene system. No polymorphism at -1663 ins/del T was observed in any subject. Linkage disequilibrium was shown between -1997T > G and -1363C > G. The frequency of haplotype -1997T/-1363C was significantly higher in patients than that in controls. The putative promoters containing -1997T/-1363C resulted in higher reporter gene activity in LX-2. Strong transcriptional inhibition by IFN gamma was shown in both cells. The T allele at -1997 of COL1A1 is crucial to the increased transcriptional activity. COL1A1 gene polymorphism might be associated with liver fibrogenesis.
引用
收藏
页码:369 / 376
页数:8
相关论文
共 35 条
[1]   Characterization of human Collagen XVIII promoter 2: Interaction of Sp1, Sp3 and YY1 with the regulatory region and a SNP that increases transcription in hepatocytes [J].
Armelin-Correa, LM ;
Lin, CJ ;
Barbosa, A ;
Bagatini, K ;
Winnischofer, SMB ;
Sogayar, MC ;
Passos-Bueno, MR .
MATRIX BIOLOGY, 2005, 24 (08) :550-559
[2]   Genetic polymorphisms and the progression of liver fibrosis: A critical appraisal [J].
Bataller, R ;
North, KE ;
Brenner, DA .
HEPATOLOGY, 2003, 37 (03) :493-503
[3]   Transcriptional activation of the type I collagen genes COL1A1 and COL1A2 in fibroblasts by interleukin-4:: Analysis of the functional collagen promoter sequences [J].
Büttner, C ;
Skupin, A ;
Rieber, EP .
JOURNAL OF CELLULAR PHYSIOLOGY, 2004, 198 (02) :248-258
[4]   The DNA binding protein BTEB mediates acetaldehyde-induced, Jun N-terminal kinase-dependent αI(I) collagen gene expression in rat hepatic stellate cells [J].
Chen, AP ;
Davis, BH .
MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (08) :2818-2826
[5]   Hepatitis B virus-related cirrhosis: Natural history and treatment [J].
Chu, CM ;
Liaw, YF .
SEMINARS IN LIVER DISEASE, 2006, 26 (02) :142-152
[6]   Pedigree disequilibrium tests for multilocus haplotypes [J].
Dudbridge, F .
GENETIC EPIDEMIOLOGY, 2003, 25 (02) :115-121
[7]  
GAO CF, 1999, J MED COLL PLA, V14, P12
[8]  
Gao CF, 2004, WORLD J GASTROENTERO, V10, P1447
[9]   In vitro functional assay of alleles and haplotypes of two COL1A1-promoter SNPs [J].
García-Giralt, N ;
Enjuanes, A ;
Bustamante, M ;
Mellibovsky, L ;
Nogués, X ;
Carreras, R ;
Díez-Pérez, A ;
Grinberg, D ;
Balcells, S .
BONE, 2005, 36 (05) :902-908
[10]   Inhibition of collagen gene expression by interferon-γ:: Novel role of the CCAAT/enhancer binding protein β (C/EBPβ) [J].
Ghosh, AK ;
Bhattacharyya, S ;
Mori, Y ;
Varga, J .
JOURNAL OF CELLULAR PHYSIOLOGY, 2006, 207 (01) :251-260