Population differences in DNA sequence variation and linkage disequilibrium at the PON1 gene.
Polymorphisms of the promoter region (-108C/T) and the coding region (192Q/R) of the paraoxonase 1 gene (PON1) showed differences in association with cardiovascular disease risk in various populations. To characterize the genetic variation underlying these important polymorphisms, we examined DNA sequence variation both in a 1.3-kb promoter region 16.5 kb from codon 192, and in a 1.7-kb region centered on the 192Q/R polymorphic site of the coding region of PON1, in 30 Africans, 30 Europeans and 64 Japanese. We found 10 polymorphic sites and 11 haplotypes in the 1.3-kb promoter region and 10 biallelic polymorphic sites and 10 haplotypes in the 1.7-kb region. From the PON1 sequences of chimpanzees and an orangutan, the ancestral type of codon 192 was found to be R. The number of pairs of polymorphic sites between the promoter and 1.7-kb regions that were in significant linkage disequilibrium was much higher in a Japanese population than in African and European populations. In addition, the pairs of polymorphic sites in linkage disequilibrium differed among the three populations. These results suggest that some of the population differences in association with risk for coronary heart disease can be explained by population differences in haplotype frequency of PON1 haplotypes.
Department of Forensic Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan. ykoda@med.kurume-u.ac.jp
Y
Y
Koda
H
H
Tachida
M
M
Soejima
O
O
Takenaka
H
H
Kimura
D000483:Alleles; D000818:Animals; D043303:Aryldialkylphosphatase / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D044383:Black People / Q000235:genetics; D003327:Coronary Disease / Q000235:genetics; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D002679:Pan troglodytes / Q000235:genetics; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011148:Pongo pygmaeus / Q000235:genetics; D011401:Promoter Regions, Genetic; D044469:Racial Groups / Q000235:genetics*; D044465:White People / Q000235:genetics
D043303:Aryldialkylphosphatase; C468406:PON1 protein, human