Proteomic and genomic studies of non-alcoholic fatty liver disease - clues in the pathogenesis

Table 2 Genomic studies of non-alcoholic fatty liver disease

Gene categories	Genes	Ref.	Year	Findings	Implications
Gene that affect lipolysis	PNPLA3	Romeo et al[91]	2008	PNPLA3 polymorphism is strongly associated with the pathogenic status of NAFLD in different populations	A well established link between PNPLA3 and NAFLD progression
		Sookoian et al[94]	2011	GG genotype of PNPLA3 (rs738409; I148M) exerts a stronger effect on hepatic lipids accumulations	Identified the patients group who is more susceptible to aggressive diseases
		Dubuquoy et al[95]	2013	PNPLA3 polymorphism is more likely to influence lipid content and liver disease severity but not insulin resistance	A less clear association of insulin resistance with PNPLA3 polymorphism
	ATGL	Chitraju et al[102]	2013	Demonstrated that ATGL-KO animal models have high insulin sensitivity	An accumulation of TG could be a protective mechanism in NAFLD
	ApoC3	Petersen et al[106]	2010	ApoC3 polymorphism is associated with NAFLD and insulin resistance in Indian populations	Highlighted the ethnic differences in ApoC3 polymorphism and disease susceptibility
		Hyysalo et al[107]	2012	ApoC3 polymorphism does not associated with NAFLD in Finnish populations
	GCKR	Santora et al[108]	2012	GCKR polymorphism is associated with NAFLD	Lipogenesis pathway plays a role in NAFLD pathogenesis
		Tan et al[112]	2013	Interactions of GCKR and PNPLA3 genes can increase susceptibility to NAFLD
	PPARGC1A and PPAR-γ	Hui et al[116]	2008	PPARGC1A gene polymorphism is not associated with NAFLDPPAR-α is associated with NAFLD susceptibility	The PGC-1α and PPAR-γ pathway play a role in NAFLD progression The role of PCG-1α (encoded by the PPARGC1A gene) in MetS is less clear than PPAR-γ
		Gawrieh et al[119]	2012	PPAR-γ polymorphism is associated with NAFLD
Genes that affect adipokines	Adiponectin	Musso et al[126]	2008	Adiponectin gene polymorphism is associated with the presence of NAFLD	De novo lipogenesis plays a role in NAFLD
		Han et al[130]	2011	Adiponectin gene polymorphism does not influence the development of T2DM	Possibility of different mechanisms for insulin sensitising in NAFLD
		Li[20]	2012
		Muhidin et al[134]	2012	Demonstrated a correlation between NAFLD and colorectal cancer	Raises the possibility and association of anti-inflammatory effect in NAFLD progression and oncological disease
	LEP and LEPR	Zain et al[139]	2013	Demonstrated an association between variants of LEPR and PNPLA3	Patients with mutations of both LEPR and PNPLA3 are highly susceptible to NAFLD
Genes that affect cytokines	TNF-α	Wang et al[142]	2012	Polymophisms of TNF-α are associated with the susceptibility to NAFLD	Insulin resistance and hepatic inflammation are relatedInsulin signal transduction pathway does contribute to the progression of NAFLD
	IL-6	Carulli et al[146]	2009	Polymorphisms of IL-6 are more prevalent in NAFLD and associated with insulin resistance
		Giannitrapani et al[145]	2013	Polymorphisms of IL-6 are unlikely to associate with insulin resistance

NAFLD: Non-alcoholic fatty liver disease; MetS: Metabolic syndrome; NASH: Non-alcoholic steatohepatitis; HCC: Hepatocellular carcinoma; CPS1: Carbamoyl phosphate synthase 1; hs-CRP: High sensitivity C-reactive protein; PTX-3: Pentraxin 3; ECM: Extracellular matrix; MMP: Matrix metalloproteinases; CCL2/MCP1: CC-chemokine ligand 2/monocyte chemo-attractant protein-1; T2DM: Type II diabetes mellitus; PPAR-γ: Peroxisome proliferator activated receptor gamma.