Non-alcoholic fatty liver disease and type 2 diabetes mellitus: The liver disease of our age?

Table 3 Single nucleotide polymorphisms associated with non-alcoholic fatty liver disease in genome wide association studies

Region	SNPs	Reported gene(s)	Mapped gene	OR	Risk allele frequency in controls	P value	Gene product function	Context	Initial sample size	Replication sample size	Platform (SNPs passing QC)	Ref.
22q13.3	rs738409 (I148M), rs2896019-G	PNPLA3	PNPLA3	2.02	0.450	2 × 10-20	Adiponutrin (PNPLA3)–nutritionally regulated lysophosphatidic acyltransferase: expressed in liver and adipose tissue. High CH diet increases expression. Has TAG hydrolase and DG transacylase activity. Strong predictor of steatosis, inflammation and fibrosis. Dysfunctional PNPLA3 promotes accumulation of lipotoxic substrates. I148M–association with HCC in severely obese individuals	Intron	392 Japanese cases, 934 Japanese controls	172 Japanese cases, 1012 Japanese control	Illumina [261540]	[119,120]
	rs738491, rs3761472, rs2143571	SAMM50	SAMM50
	rs6006473, rs5764455, rs6006611	PARVB	PARVB
1p35	rs6691847-C	PTPRU	PTPRU - MATN1	1.32	0.770	7 × 10-6	Member of the protein tyrosine phosphatase (PTP) family. PTPs are signaling molecules that regulate cell growth, differentiation, mitotic cycle, and oncogenic transformation
4q13.3	rs222054-C	GC	LDHAL6EP - GC	2.54	0.301	1 × 10-6	Albumin gene family. Multifunctional protein found in plasma, ascitic fluid, cerebrospinal fluid and on the surface of many cell types. It binds to vitamin D and its plasma metabolites and transports them to target tissues		126 European adolescent cases - 802 European adolescent controls	NR	Illumina [2078805] (imputed)	[142]
16q23	rs11864146-A	SLC38, A8	SLC38A8	3.14	0.100	2 × 10-6	Amino acid transport: Putative sodium-coupled neutral amino acid transporter 8	Intron
13q14.1	rs7324845-A	LCP1	LCP1	3.29	0.096	3 × 10-6	L-plastin, an actin binding protein expressed in hemopoetic cell lineages. It is expressed by many solid tumor types of non-hemopoetic origin, suggesting its role in tumorigenesis	Intron
1p21	rs12743824-C	LPPR4	LPPR4 - PALMD	2.30	0.441	5 × 10-6	LPPR4: a lipid phosphate phosphatase, catalyzes the dephosphorylation of a number of bioactive lipid mediators, found to be important for axonal outgrowth; PALMD: cytosolic isoform of paralemmin-1, a lipid raft-associated protein implicated in cell shape control	NR				PALMD gene product - [143]
7p14	rs343064-A	Intergenic	TBX20-HERPUD2	1.31	0.400	3 × 10-8	TBX20: transcription factor; HERPUD2: not reported		236 non-Hispanic Caucasian women	NR	Illumina [324623]	SNPs of other genes were also associated with qulatitative traits (e.g. NAFLD activity score and FDFT1 - rs2645424) as discussed in the text [123]
2q31	rs1529093-A	Intergenic	RPL29P8 - KRT8P40	4.13	0.410	2 × 10-6	RPL29P8, KRT8P40: pseudogenes			NR	Illumina [324623]
4p15.2	rs959903-A	23231	SEL1L3	3.81	0.290	7 × 10-6		Intron		NR	Illumina [324623]

Not all GWAS studies were replicated. Risk gene variants with OR higher than 1.31 are indicated in the table. Based on the National Human Genome Research. SNPs: Single nucleotide polymorphisms; NR: Not reported.