The association of reduced LAL activity with the premature development of coronary artery disease has been demonstrated in patients with hypercholesterolemia, and in the present study we show for the first time that LAL expression is suppressed in monocytes from patients with Lp(a) hyperlipidemia and by purified Lp(a).
Genotype rs2246942-GG of the LIPA gene was associated with an increased risk of CHD [CHD cases versus healthy controls: P=0.04; odds ratio (OR)=1.63; 95% confidence interval (CI)=1.02-2.60).
Future studies will continue to focus on the role of LAL in the crosstalk between lipid metabolism and cellular function in health and diseases including coronary heart disease.
Our findings show that common LIPA exonic variants in the signal peptide are of minimal functional significance and suggest coronary artery disease risk is instead associated with increased LIPA function linked to intronic variants.