Functional characterization of 4 polymorphisms in promoter region of hepatic lipase gene

Hepatic lipase (HL) is a lipolytic enzyme involved in the metabolism of pla sma lipoproteins, especially high density lipoproteins. Association studies have provided strong evidence for relations of common mutations in the pro moter region of the HL gene to postheparin plasma HL activity and the plasm a high density lipoprotein cholesterol concentration, but the functional re levance of these polymorphisms has not been evaluated to date, We analyzed the physiological significance of 4 common polymorphisms (-250G/A, -514C/T, -710T/C, and -763A/G, all in strong linkage disequilibrium) in the promote r of the HL gene by use of electrophoretic mobility shift assays and transi ent transfection studies in HepG2 cells. No consistent evidence was found f or a significant contribution of any of these polymorphisms to the basal ra te of transcription of the HL gene. These data suggest that the 4 polymorph isms in the promoter region of the HL gene are in linkage disequilibrium wi th greater than or equal to 1 as-yet-unknown functional polymorphisms in th e HL gene locus with a significant effect: on HL metabolism and/or enzymati c activity.