Identification of a candidate genetic variant for the high prevalence of type II diabetes in Polynesians.
The prevalence of non-insulin-dependent diabetes mellitus (type II diabetes) in Polynesia is among the highest recorded worldwide and is substantially higher than in neighboring human populations. Such large differences in the frequency of a phenotype between populations may be explained by large allele frequency differences between populations in genes associated with the phenotype. To identify genes that may explain the high between-population variation in type II diabetes prevalence in the Pacific, we determined the frequency of 10 type II diabetes-associated alleles in 23 Polynesians, 23 highland New Guineans and 19 Han Chinese, calculated population-pairwise Fst values for each allele and compared these values to the distribution of Fst values from approximately 100,000 SNPs from the same populations. The susceptibility allele in the PPARGC1A gene is at a frequency of 0.717 in Polynesians, 0.368 in Chinese but is absent in the New Guineans. The striking frequency difference between Polynesians and New Guineans is highly unusual (Fst=0.703, P=0.007) and we therefore suggest that this allele may play a role in the large difference in type II diabetes prevalence between Polynesians and neighboring populations.
Myles
Sean
S
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany. myles@eva.mpg.de
Hradetzky
Eva
E
Engelken
Johannes
J
Lao
Oscar
O
Nürnberg
Peter
P
Trent
Ronald J
RJ
Wang
Xingyu
X
Kayser
Manfred
M
Stoneking
Mark
M
D000483:Alleles; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D020641:Polymorphism, Single Nucleotide; D011114:Polynesia / Q000453:epidemiology; D011153:Population / Q000235:genetics*; D015995:Prevalence; D014157:Transcription Factors / Q000235:genetics*
D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors