Prevalence of UGT1A9 and UGT2B7 nonsynonymous single nucleotide polymorphisms in West African, Papua New Guinean, and North American populations.
OBJECTIVE
UDP-glucuronosyltransferases (UGTs) UGT1A9 and UGT2B7 are involved in the metabolism of antimalarial dihydroartemisinin and antiretroviral zidovudine. Our aim was to analyze the prevalence of UGT1A9 (chromosome 2) and UGT2B7 (chromosome 4) nonsynonymous single nucleotide polymorphisms (SNPs) in West African (WA), Papua New Guinean (PNG), and North American (NA) populations.


METHODS
Using a post-PCR ligation detection reaction-fluorescent microsphere assay, frequencies of UGT1A9 (8G > A, 98T > C, 766G > A) and UGT2B7 (211G > T, 802C > T, 1192G > A) SNPs were determined in WA (n = 133, 5 countries), PNG (n = 153), and NA (n = 350, 4 ethnic groups) individuals.


RESULTS
The UGT1A9 variant alleles were not common in the study populations. None of the SNPs were present in WA and PNG. Among NA, all 3 SNPs were present (1% each) in Asian-Americans, while 98T > C was present only in Caucasian-Americans (1%) and Hispanic-Americans (1%). Regarding UGT2B7 SNPs, the prevalence of 802C > T was 21% in WA, 28% in PNG, and 28-52% in NA. The SNP 211G > T was present only in Asian-Americans (9%) and Hispanic-Americans (2%), while 1192G > A was not present in any of the subjects. No significant linkage was observed at UGT1A9, UGT2B7, and between both the loci in any of the study populations.


CONCLUSIONS
Taken together, the UGT1A9-UGT2B7 polymorphism profile in WA and PNG populations is similar to African-Americans, but different from Asian-Americans. It is important to determine if these differences, along with previously reported differences in cytochrome P450 2B6 allele frequencies, are associated with altered metabolism/effectiveness of artemisinin drugs.
Mehlotra
Rajeev K
RK
Center for Global Health and Diseases, Case Western Reserve University, School of Medicine, Wolstein Research Building #4204, 2103 Cornell Road, Cleveland, OH 44106-7286, USA. rkm@case.edu
Bockarie
Moses J
MJ
Zimmerman
Peter A
PA
D000349:Africa / Q000208:ethnology; D044466:Asian People; D044383:Black People; D019353:Endemic Diseases; D005787:Gene Frequency; D014453:Glucuronosyltransferase / Q000235:genetics*; D006239:Haplotypes; D006630:Hispanic or Latino; D006801:Humans; D008288:Malaria / Q000208:ethnology; D009656:North America / Q000208:ethnology; D010219:Papua New Guinea / Q000208:ethnology; D020641:Polymorphism, Single Nucleotide; D044382:Population Groups; D000090264:UDP-Glucuronosyltransferase 1A9; D044465:White People; D001741:Black or African American
C000715591:UGT1A9 protein, human; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase; D000090264:UDP-Glucuronosyltransferase 1A9