Extent of linkage disequilibrium between the androgen receptor gene CAG and GGC repeats in human populations: implications for prostate cancer risk.
While studies have implicated alleles at the CAG and GGC trinucleotide repeats of the androgen receptor gene with high-grade, aggressive prostate cancer disease, little is known about the normal range of variation for these two loci, which are separated by about 1.1 kb. More importantly, few data exist on the extent of linkage disequilibrium (LD) between the two loci in different human populations. Here we present data on CAG and GGC allelic variation and LD in six diverse populations. Alleles at the CAG and GGC repeat loci of the androgen receptor were typed in over 1000 chromosomes from Africa, Asia, and North America. Levels of linkage disequilibrium between the two loci were compared between populations. Haplotype variation and diversity were estimated for each population. Our results reveal that populations of African descent possess significantly shorter alleles for the two loci than non-African populations (P<0.0001). Allelic diversity for both markers was higher among African Americans than any other population, including indigenous Africans from Sierra Leone and Nigeria. Analysis of molecular variance revealed that approx. 20% of CAG and GGC repeat variance could be attributed to differences between the populations. All non-African populations possessed the same common haplotype while the three populations of African descent possessed three divergent common haplotypes. Significant LD was observed in our sample of healthy African Americans. The LD observed in the African American population may be due to several reasons; recent migration of African Americans from diverse rural communities following urbanization, recurrent gene flow from diverse West African populations, and admixture with European Americans. This study represents the largest genotyping effort to be performed on the two androgen receptor trinucleotide repeat loci in diverse human populations.
Kittles
R A
RA
National Human Genome Center, Howard University, 2041 Georgia Ave., Washington, DC 20060, USA. rkittles@howard.edu
Young
D
D
Weinrich
S
S
Hudson
J
J
Argyropoulos
G
G
Ukoli
F
F
Adams-Campbell
L
L
Dunston
G M
GM
D000349:Africa / Q000208:ethnology; D001741:Black or African American; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001208:Asia; D044383:Black People; D014644:Genetic Variation; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D009656:North America; D011471:Prostatic Neoplasms / Q000235:genetics*; D011944:Receptors, Androgen / Q000235:genetics*; D012307:Risk Factors; D018911:Trinucleotide Repeats
D011944:Receptors, Androgen