Study of the Association Between Polymorphisms of the COL1A1 Gene and HBV-Related Liver Cirrhosis in Chinese Patients
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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 IFNγ 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.
KeywordsCirrhosis Fibrosis Collagen Polymorphism Promoter
This work was supported by the National Natural Science Foundation of China (No. 30270605 and No. 30571774). The authors are grateful for the kindly supply of LX-2 cell line by Professor Dr Scott L. Friedman from the USA.
- 1.Gressner AM, Schuppan D (1999) Cellular and molecular pathobiology, pharmacological intervention, and biochemical assessment of liver fibrosis. In: Bircher J, Benhamou J-P, McIntyre N, Rizzetto M, Rodes J (eds) Clinical hepatology, vol 1, 2nd edn. Oxford Medical Publications, Oxford, pp 607–627Google Scholar
- 3.Okazaki I, Yonezawa Y, Watanabe T, Mayne R, Ninomiya T (2003) New insights into the extracellular matrix. In: Okazaki I, Ninomiya Y, Friedman SL, Tanikawa K (eds) Extracellular matrix and the liver. Academic Press, Elsevier Science, pp 3–22Google Scholar
- 5.Tanaka K, Matsumoto Y, Nakatani F, Iwamoto Y, Yamada Y (2000) A zinc finger transcription factor, alphaA-crystallin binding protein 1, is a negative regulator of the chondrocyte-specific enhancer of the alpha1(II) collagen gene. Mol Cell Biol 20:4428–4435. doi: 10.1128/MCB.20.12.4428-4435.2000 PubMedCrossRefGoogle Scholar
- 6.Hasegawa T, Takeuchi A, Miyaishi O, Xiao H, Mao J, Isobe K (2000) PTRF (polymerase I and transcript-release factor) is tissue-specific and interacts with the BFCOL1 (binding factor of a type-I collagen promoter) zinc-finger transcription factor which binds to the two mouse type-I collagen gene promoters. Biochem J 347(Pt 1):55–59. doi: 10.1042/0264-6021:3470055 PubMedCrossRefGoogle Scholar
- 10.Gao CF, Wang H, Wu YA, Kong XT (1999) Effect of cytokines on promoter activity in mouse α(I)procollagen gene. J Med Coll PLA 14:12–16Google Scholar
- 12.Marini JC, Forlino A, Cabral WA et al (2007) Consortium for osteogenesis imperfecta mutations in the helical domain of type I collagen: regions rich in lethal mutations align with collagen binding sites for integrins and proteoglycans. Hum Mutat 28:209–221. doi: 10.1002/humu.20429 PubMedCrossRefGoogle Scholar
- 23.Papakrivopoulou J, Lindahl GE, Bishop JE, Laurent GJ (2004) Differential roles of extracellular signal-regulated kinase 1/2 and p38(MAPK) in mechanical load-induced procollagen alpha(1)(I) gene expression in cardiac fibroblasts. Cardiovasc Res 61:736–744. doi: 10.1016/j.cardiores.2003.12.018 PubMedCrossRefGoogle Scholar
- 24.Tsukada S, Westwick JK, Ikejima K, Sato N, Rippe RA (2005) SMAD and p38 MAPK signaling pathways independently regulate alpha1(1)collagen gene expression in unstimulated and transforming growth factor-beta-stimulated hepatic stellate cells. J Biol Chem 280:10055–10064. doi: 10.1074/jbc.M409381200 PubMedCrossRefGoogle Scholar
- 35.Armelin-Correa LM, Lin CJ, Barbosa A et al (2005) 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. Matrix Biol 24:550–559. doi: 10.1016/j.matbio.2005.08.003 PubMedCrossRefGoogle Scholar