Genetic, metabolic and environmental factors involved in the development of liver cirrhosis in Mexico

Table 1 Genetic polymorphisms associated with alcohol dependence, alcohol abuse and liver disease

Gene	Risk allele	Association	Population	Ref.
Alcohol-metabolizing enzymes
CYP2E1	CYP2E1*c2	Higher susceptibility to LC; decompensated liver function	Mexican (Mestizo), West Mexico	[110]
ADH1B	ADH1B*2	Higher risk to LC	Japanese	[111]
ADH1B	ADH1B*1	Alcohol dependence	European, Asian	[112-114]
ALDH2	ALDH2*1	Higher susceptibility to LC	Japanese	[111]
Alcohol dependence genes
DRD2	Taq I A1	Alcohol dependence	European, East Asian	[115]
TAS2R38	AVV haplotype	Higher alcohol intake	Mexican, (Mestizo), West Mexico	[39]
Lipid metabolism
APOE	APOE*2	Hypertriglyceridemia and increased development of early LC	Mexican (Mestizo), West Mexico	[36]
FABP2	Ala54	Earlier onset of LC	Mexican (Mestizo), West Mexico	[116]
PNPLA3	M148	Alcoholic liver disease and clinically evident LC	Mixed European and Native American, Mexico City	[117,118]
PPAR-γ2	Ala12	Increased risk to develop severe steatohepatitis and fibrosis	German	[119]
Immune response
TNF-α	-238 A	Higher prevalence of LC	Spanish	[120]
NF-ΚB	ATTG deletion	Higher prevalence of LC	Spanish	[121]
CXCL1	rs4074 A	Higher prevalence of LC	German	[122]
CD14	-159 T	Advanced liver disease, hepatitis and especially with LC	Finnish	[123,124]

LC: Liver cirrhosis.

Table 2 Genetic polymorphisms associated with the outcomes of hepatitis C virus infection

Gene	Risk allele	Association	Population	Ref.
Lipid metabolism
APOB	-516 C	Increased susceptibility of HCV infection	Chinese	[125]
APOE	APOE*3	Viral persistence	Northern European	[126]
LDLr	rs2738459 C, rs2569540 G, rs1433099 A, rs11672123 A	Higher viral load in genotypes 1 and 4	Spanish	[127]
MTTP	-493 T	Higher degree of steatosis, HCV RNA serum levels and hepatic fibrosis	Native Italian	[128,129]
PNPLA3	M148	Higher risk for steatosis and fibrosis progression	European: Belgian, German and French	[130]
Inmune response mediators
CXCL1	rs4074 A	Higher risk for LC	German	[131]
IL-28B	rs12979860 T	Higher risk for LC and HCC	Native Italian and Chinese	[132,133]
TGF-β1	-509 T	Higher risk for LC and HCC	Egyptian	[134]
TNF-α	-308 A	Higher risk for LC and HCC	Egyptian	[134]
Fibrogenesis
MMP-1	-1607 2G	Higher prevalence of LC	Japanese	[135]
MMP-3	-1171 5A	Lower age at LC diagnosis and a higher Child-Pugh score	Japanese	[135]
MMP-9	-1562 C	Higher prevalence of LC	Japanese	[135]
Nutrient metabolism
MTHFR	677 T	Hyperhomocysteinemia and higher degree of steatosis and fibrosis	Italian	[136]
HFE	63 D	Higher likelihood of LC	Taiwanese	[137]
VDR	CAA haplotype (rs1544410 C, rs7975232 A, rs731236 A)	Higher fibrosis progression and LC	Swiss	[138]

LC: Liver cirrhosis; HCV: Hepatitis C virus; HCC: Hepatocellular carcinoma.

Table 3 Genetic polymorphisms associated with the outcomes of hepatitis B virus infection

Gene	Risk allele	Association	Population	Ref.
Immune response mediators
IL-10	-592 C	Significant increased risk of LC	Asian	[139]
IL-28B	rs12979860 C	Increased risk for developing LC	Asian	[140]
TGF-β1	10 T	Higher prevalence of LC	Chinese	[141]
TGF-β1	-509 C	Higher susceptibility to LC	Chinese	[142]
Fibrogenesis
COL1A1	TC haplotype (-1997 T, -1363 C)	Higher prevalence of LC	Chinese	[143]
COL3A1	rs3106796 A	Higher prevalence of chronic hepatitis, LC and HCC	Koreans	[144]

LC: Liver cirrhosis; HCC: Hepatocellular carcinoma.

Table 4 Genetic polymorphisms associated with the development of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

Gene	Risk allele	Association	Population	Ref.
Lipid metabolism
APOC3	482 T, 455 C	Higher fasting plasma triglyceride concentration and higher prevalence of NAFLD	Asian Indian	[145]
PNPLA3	M148	Increased hepatic fat levels, hepatic inflammation and fibrosis in NAFLD and NASH patients	Hispanic, African American, European American, Finnish, Argentinean, Italian	[146-150]
MTTP	-493 G	Higher intrahepatic triglycerides content. Higher incidence and progression of NASH	French, Japanese	[151,152]
PEMT	M175	Higher prevalence of NAFLD and NASH	Hispanic, African American, European American, Asian	[153,154]
Insulin resistance/sensitivity
ADIPOQ	45 T, 276 T	Higher prevalence of NAFLD. Lower postprandial adiponectin and higher postprandial triglyceride, VLDL, and FFA in NASH patients	Italian	[155]
	45 G, 276 G	Higher prevalence of NAFLD, severe fibrosis and insulin resistance in females	Japanese	[156]
ADIPOR1	-8503 A, -1927 C	Lower insulin sensitivity and higher liver fat	German	[157]
ADIPOR2	rs767870 T	Increased hepatic fat and biochemical surrogates of NAFLD	Finnish	[158]
PPAR-γ	161 T	Higher susceptibility of NAFLD	Chinese	[159]
PPARGC1A	rs2290602 T	Higher occurrence of NAFLD	Japanese	[160]
PPAR-α	Val227	Higher prevalence of NAFLD and anthropometrical indicators of obesity	Chinese	[161]
Oxidative stress
GCLC	-129 T	Higher prevalence of NASH	Brazilian	[162]
NOS2	rs1060822 T	Higher fibrosis index in NAFLD patients	Japanese	[163]
SOD2	1183 T	Higher prevalence of NASH	Japanese	[152]
Immune response mediators
STAT3	rs6503695 T, rs9891119 A	Higher prevalence of NAFLD	Argentinean	[164]
TNF-α	-238 A	Higher prevalence of NAFLD and NASH	Italian, Chinese	[165,166]
IL-8	-251 A	Disease progression in NASH	Turkish	[167]
IL-6	-174 C	Higher risk for NAFLD and NASH	Italian	[168]
MTHFR	1298 C, 677 C	Higher prevalence of NASH	Turkish	[169]
HFE	282 Y	More hepatic fibrosis in NASH patients. Higher prevalence of NAFLD	Australian	[170-172]
ABCC2/MRP2	rs17222723 T, rs8187710 A	NAFLD disease severity	Argentinean	[173]
AGTR1	rs3772633 G, rs3772627 C, rs3772622 A	Higher prevalence of NASH	Japanese	[174]

NAFLD: Nonalcoholic fatty liver disease; NASH: Nonalcoholic steatohepatitis.