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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:2672-2678.)
© 1997 American Heart Association, Inc.

Articles

Ethnic Variation and In Vivo Effects of the -93tg Promoter Variant in the Lipoprotein Lipase Gene

Ewa Ehrenborg; Susanne M. Clee; Simon N. Pimstone; Paul W.A. Reymer; Pascale Benlian; Christiaan F. Hoogendijk; Henry J. Davis; Nagat Bissada; Li Miao; S. Eric Gagné; L. Jacquie Greenberg; Ronald Henry; Howard Henderson; José M. Ordovas; Ernst J. Schaefer; Johannes J.P. Kastelein; Maritha J. Kotze; ; Michael R. Hayden

From the Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada (E.E., S.M.C., S.N.P., P.B., N.B., L.M., S.E.G., M.R.H.), the Lipid Research Group, Academic Medical Centre, Amsterdam, The Netherlands (P.W.A.R., R.H., J.J.P.K.), the Division of Human Genetics, University of Stellenbosch, Tygerberg, South Africa (C.F.H., H.J.D., M.J.K.), the Department of Human Genetics, University of Cape Town Medical School, Cape Town, South Africa (L.J.G.), the Department of Chemical Pathology, Red Cross Children's Hospital, Cape Town, South Africa (H.H.), and JM-USDA-HNRCA at Tufts University, Boston, Mass (J.M.O., E.J.S.).

Correspondence to Michael R. Hayden, Department of Medical Genetics, University of British Columbia, 416-2125 East Mall, NCE Building, Vancouver, British Columbia V6T 1Z4, Canada. E-mail mrh{at}ulam.generes.ca

Abstract Recently, a (tg) transition at nucleotide -93 in the lipoprotein lipase (LPL) gene promoter has been observed in Caucasians. Here, we have compared the frequency of the -93g carriers in three distinct populations (Caucasians, South African Blacks, and Chinese). The carrier frequency in the Caucasian population was 1.7% (4/232), which was in contrast to the South African Black population, which had a frequency for this allele of 76.4% (123/161) of the individuals tested. This transition was not observed in the Chinese population under study. Near complete linkage disequilibrium between the -93g and the previously described D9N mutation was observed in the Caucasian population but not in South African Blacks. To further assess the ancestral origins of these DNA changes, DNA haplotyping using a CA repeat 5' to these substitutions was performed. The -93t allele was associated with only a few specific dinucleotide repeat sizes. In contrast, the -93g allele occurred on chromosomes with many different repeat lengths. The broad distribution of repeats on -93g carrying chromosomes, their high frequency in the South African Black population, and the conservation of the -93g allele among different species may suggest that the -93g allele is the ancestral allele on which a transition to t and the D9N mutations arose. The very high frequency of the -93g allele distinct from the N9 allele in a cohort of Black South Africans allowed us to specifically assess the phenotypic effects of the -93g allele on lipids. Individuals homozygous for the g allele at -93 showed mildly decreased triglycerides compared with individuals homozygous for the t allele (1.14±0.66 mmol/L versus 0.82±0.3; P=.04). Thus, the -93g allele in this cohort is associated with low plasma triglyceride levels.

Key Words: lipoprotein lipase • mutation • promoter • lipids • ethnic variation

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