title: Ethnic variation and in vivo effects of the -93t-->g promoter variant in the lipoprotein lipase gene.
abstract: Recently, a (t-->g) 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.
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Ehrenborg
authors.forename: S M
authors.initials: SM
authors.lastname: Clee
authors.forename: S N
authors.initials: SN
authors.lastname: Pimstone
authors.forename: P W
authors.initials: PW
authors.lastname: Reymer
authors.forename: P
authors.initials: P
authors.lastname: Benlian
authors.forename: C F
authors.initials: CF
authors.lastname: Hoogendijk
authors.forename: H J
authors.initials: HJ
authors.lastname: Davis
authors.forename: N
authors.initials: N
authors.lastname: Bissada
authors.forename: L
authors.initials: L
authors.lastname: Miao
authors.forename: S E
authors.initials: SE
authors.lastname: Gagné
authors.forename: L J
authors.initials: LJ
authors.lastname: Greenberg
authors.forename: R
authors.initials: R
authors.lastname: Henry
authors.forename: H
authors.initials: H
authors.lastname: Henderson
authors.forename: J M
authors.initials: JM
authors.lastname: Ordovas
authors.forename: E J
authors.initials: EJ
authors.lastname: Schaefer
authors.forename: J J
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: M J
authors.initials: MJ
authors.lastname: Kotze
authors.forename: M R
authors.initials: MR
authors.lastname: Hayden
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D002681:China / Q000208:ethnology; D002784:Cholesterol / Q000097:blood; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D018900:Dinucleotide Repeats; D005006:Ethnicity / Q000235:genetics*; D005787:Gene Frequency; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics; D008072:Hyperlipoproteinemia Type I / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D010641:Phenotype; D017354:Point Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013019:South Africa / Q000208:ethnology; D014280:Triglycerides / Q000097:blood; D044465:White People / Q000235:genetics*; D001741:Black or African American
chemical_list: D014280:Triglycerides; D002784:Cholesterol; D008071:Lipoprotein Lipase