rs2228603 is a SNP in the NCAN gene (also known as CSPG3), coding for the neurocan core protein. The T risk allele results in a proline to serine missense mutation at position 92 of the protein.
In a large GWAS of individuals of European descent published in March, 2011, rs2228603 was found to be associated with nonalcoholic fatty liver disease (NAFLD), as evidenced by hepatic steatosis found by CT scanning and confirmed by histology. The investigators confirmed their initial findings with using the same case cohort and two separate control groups and found genome-wide significant odds ratios of 1.65 (95% CI = 1.15-2.87; p=5.29E-5; p=6.82E-10) and 1.9 (95% CI not reported) NAFLD is associated with higher LDL-C and lower LDL-C levels as well as impaired fasting glucose and increased risk of insulin resistance and diabetes. However, rs2228603 was found to be associated with lower triglycerides and plasma LDL-Cholesterol in this study [PMID 21423719].
[PMID 22719876] Genetic Polymorphisms of the Human PNPLA3 Gene Are Strongly Associated with Severity of Non-Alcoholic Fatty Liver Disease in Japanese
[PMID 18193044] Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans.
[PMID 18852197] Metabolic and cardiovascular traits: an abundance of recently identified common genetic variants.
[PMID 19802338] Genetic loci associated with plasma concentration of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A1, and Apolipoprotein B among 6382 white women in genome-wide analysis with replication.
[PMID 24477042] Genetic variants in GCKR and PNPLA3 confer susceptibility to nonalcoholic fatty liver disease in obese individuals
[PMID 24946282] A common polymorphism in the NCAN gene is associated with hepatocellular carcinoma in alcoholic liver disease