Non invasive fibrosis biomarkers reduce but not substitute the need for liver biopsy

Table 2 Gene polymorphisms described as involved in fibrogenesis

Author	Etiologyof liver disease	Gene	Function ofthe gene product	Implicatedgenotype	Effect ongene product	Effecton fibrosis
Powell[39]	HCV	TGF-β1	Profibrogenic	Codon 25 (pro/arg)	Increased transcription	Increased
Powell[39] Forrest[40]	HCV	AT	Profibrogenic	-6 G/A	Increased transcription	Discordant results
Bonkovsky[41] Negro[42] Chitturi[43] Geier[44]	HCV / NASH	HFE	Iron metabolism	C282Y, H63D	Iron overload	Discordant results
Yee[45] Grove[46]	HCV /AFLD	TNF-β	Proinflammatory	-308 G/A	Increased transcription	Increased
Grove[47] Knapp[48]	HCV / AFLD	IL-10	Immune modulation	-1082 A/A; -627 C/A	Decreased transcription	Increased
Reynolds[49]	HCV	MPO	Battericide	-463 G/A	Increased transcription	Increased
Wozniak[50]	HCV	ApoE	Viral entry to cells	E4 allele	Abnormal function	Reduced
Muhlbauer[51]	HCV	MCP-1	Proinflammatory	-2518 G/A	Increased transcription	Increased
Wright[52]	HCV	Factor V Leiden	Thrombine generation	Codon 560 (arg/gln)	Resistance to activation	Increased
Romero-Gomez[53]	HCV	SLC11A1	Macrophage function	Homozygosity (GT)5AC(GT)10G (Allele 2) in the promoter region	Poor promoter	Reduced
Adinolfi[54]	HCV	MTHFR	Folate metabolism	C677T	HyperHC	Increased
Okamoto[55]	HCV	MMP	Matrix degradation	1G/2G (MMP-1), 5A/6A (MMP-3), C/T (MMP-9)	Reduced transcription	More frequent in cirrhosis than CHC
Yamauchi[56] Okamoto[57] Frenzer[58]	AFLD	CYP2E1	Ethanol metabolism	c1/c1, c2/c2 alleles	Increased activity	Discordant results
Yamauchi[56] Frenzer[58]	AFLD	ADH	Ethanol metabolism	ADH2 c1,c2,c3 alleles; ADH3 c1, c2, c3 alleles	Abnormal function	Discordant results
Yamauchi[56] Okamoto[57]	AFLD	ALDH	Ethanol metabolism	ALDH2 c2/c2 alleles	Abnormal function	Discordant results
Burim[59]	AFLD	CYP1A1	Ethanol metabolism	m2/m2 allele	Increased activity	Increased
Dixon[60]	NAFLD	AT and TGF-β	Profibrogenic	High AT and TGF- β1 producing polymorphisms	Increased activity	Increased

TGF-β = transforming factor beta; AT = angiotensinogen; HFE = hereditary haemochromatosis gene; NASH = non alcoholic steatohepatitis; TNF-β = tumor necrosis factor beta; AFLD = alcoholic liver disease; IL-10 = interleukin 10; NAFLD = non alcoholic fatty liver disease; MPO = myeloperoxidase; ApoE = apolipoprotein E; MCP-1 = monocyte chemotactic protein 1; SLC11A1 = solute carrier family 11 member 1; MTHFR = methylenetetrahydrofolate reductase; HC = homocisteinemia; MMP = metalloproteinase; CYP2E1 = cytochrome P 2E1; ADH = alcohol dehydrogenase; ALDH = aldehyde dehydrogenase; CYPA1 = cytochrome P A1.