title: A common mutation in the lipoprotein lipase gene promoter, -93T/G, is associated with lower plasma triglyceride levels and increased promoter activity in vitro.
abstract: Single-strand conformational polymorphism analysis of the lipoprotein lipase promoter identified a T-->G transition at position -93. The frequency in healthy white men was 3.4% (n = 1575). There was an 83% allelic association between -93T-->G and Asp9-->Asn (D9N); all N9 mutations occurred on a -93G allele, but not all -93G mutations occurred on an N9 allele. It was thus possible to assess the effect on plasma triglyceride (Tg) levels of the rare -93G mutation in the presence of the wild-type D9. Carriers of the -93G, with genotype TG/DD, had significantly lower Tg levels than TT/DD individuals (1.36 versus 1.78 mmol/L, P = .01); carriers of both mutations (TG/DN) had the highest Tg levels (1.93 mmol/L). When the group was stratified above and below the sample mean for body mass index (BMI), carriers of the -93G on a D9 allele (TG/DD) were "protected" against the Tg-raising effect of obesity, as assessed by BMI. In Afro-Caribbeans (n = 91), the carrier frequency of -93G was 18-fold higher (63%), with weaker (17%) allelic association between -93G and N9. In vitro, the -93G promoter had 24% higher activity than the -93T in a rat smooth muscle cell line and 18% higher activity in a human adrenal cell line. A protein identified by band-shift assays bound to the -93G but not to the -93T allele, which may explain the lower Tg levels in -93G carriers.
authors.affiliation: Department of Medicine, University College London Medical School, Rayne Institute, UK.
authors.forename: S
authors.initials: S
authors.lastname: Hall
authors.forename: G
authors.initials: G
authors.lastname: Chu
authors.forename: G
authors.initials: G
authors.lastname: Miller
authors.forename: K
authors.initials: K
authors.lastname: Cruickshank
authors.forename: J A
authors.initials: JA
authors.lastname: Cooper
authors.forename: S E
authors.initials: SE
authors.lastname: Humphries
authors.forename: P J
authors.initials: PJ
authors.lastname: Talmud
mesh_terms: D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D005838:Genotype; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D051381:Rats; D014280:Triglycerides / Q000097:blood*
chemical_list: D014280:Triglycerides; D008071:Lipoprotein Lipase