Table 3 Summary of known evidence or hypothesis on the functional and biological role of metabolites for each of the three lipid loci

GCKR

Phosphatidylcholine

GCKR encodes a glucokinase regulatory protein that inhibits glucokinase in liver and pancreatic islet cells by binding non-covalently to form an inactive complex with the enzyme. The locus has been shown to have a pleiotropic effect on multiple cardio-metabolic phenotypes [15, 24, 52–56]. We postulate here that GCKR SNPs affect TC through regulation of phosphatidylcholine metabolism, a hypothesis that needs to be validated in experimental settings.

LPA

Carnitine

A connection between Lp(a) and carnitine has been shown before. Derosa et al.[57] observed a statistically significantly decreased plasma Lp(a) concentration after L-carnitine intake of up to six month . Moreover, after a coadministration of simvastatin and carnitine the reduction in Lp(a) was significanty greater than after simvastatin medication alone [58].

FADS1

Phosphatidylcholine

The FADS1-2-3 gene cluster encodes for fatty acid desaturase enzymes regulating the desaturation of fatty acids by adding double bonds between carbons of the fatty acyl chain [59–61]. Whereas FADS1 modifies the efficiency of the fatty acid delta-5 desaturase reaction, FADS2 modifies the fatty acid delta-6 desaturase reaction. GWAS of polyunsaturated fatty acids have shown associations between different fatty acids and the FADS1-2-3 gene cluster [12]. Arachidonic acid, most likely a side chain of PC aa C36:4, is presumably involved in atherosclerotic processes [62, 63].