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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:1969-1976.)
© 1997 American Heart Association, Inc.

Articles

A Common Mutation in the Lipoprotein Lipase Gene Promoter, -93T/G, Is Associated With Lower Plasma Triglyceride Levels and Increased Promoter Activity In Vitro

Stephen Hall; Grace Chu; George Miller; Kennedy Cruickshank; Jaqueline A. Cooper; Steve E. Humphries; ; Philippa J. Talmud

From the Department of Medicine, University College London Medical School, Rayne Institute (S.H., G.C., S.E.H., P.J.T.); the MRC Epidemiology and Medical Care Unit, Wolfson Institute of Preventive Medicine, The Medical College of St Bartholomew's Hospital, London (G.M., J.A.C.); and the Clinical Epidemiology Unit, University of Manchester Medical School, Manchester (K.C.), UK.

Correspondence to Dr Philippa Talmud, Division of Cardiovascular Genetics, Department of Medicine, UCL Medical School, Rayne Institute, University St, London WC1E 6JJ, UK. E-mail ptalmud{at}medicine.ucl.ac.uk

Abstract Single-strand conformational polymorphism analysis of the lipoprotein lipase promoter identified a TG transition at position -93. The frequency in healthy white men was 3.4% (n=1575). There was an 83% allelic association between -93TG and Asp₉Asn (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.

Key Words: lipoprotein lipase promoter mutation • SSCP • Afro-Caribbean • plasma triglycerides

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