STRENGTH OF LINKAGE DISEQUILIBRIUM BETWEEN 2 VITAMIN-D-RECEPTOR MARKERS IN 5 ETHNIC-GROUPS - IMPLICATIONS FOR ASSOCIATION STUDIES

Markers in the 3' end of the vitamin D receptor gene have recently bee n associated with prostate cancer risk, To evaluate the adequacy of th e commonly used BsmI restriction fragment length polymorphism as a mar ker of this locus, we genotyped 627 individuals from five ethnic group s for this marker, as well as for a polymorphic site in the 3' untrans lated region of this gene, At the latter site, we identified 12 allele s, A(13) to A(24), of a poly(A) microsatellite. Allele size followed a bimodal distribution with distinct short (A(13)-A(17)) and long (A(18 )-A(24)) allele populations, Poly(A) allele frequency differed by ethn icity, with the frequency of short alleles being highest in non-Hispan ic whites (41%), intermediate in Hispanics and African-Americans (31 a nd 29%, respectively), and lowest in Japanese-Americans and Chinese (8 and 9%, respectively), In each of the ethnic groups, some degree of c oupling was observed between BsmI B and short poly(A) alleles and betw een BsmI b and long poly(A) alleles, However, the strength of the link age disequilibrium varied by ethnicity, with departures from complete disequilibrium producing disagreement between the BsmI and poly(A) gen otypes, Genotypic disagreement was lowest in Japanese-Americans and no n-Hispanic whites (6 and 7%, respectively), intermediate in Chinese an d Hispanics (11 and 19%, respectively), and highest among African-Amer icans (37%), indicating that BsmI is not a good marker for the vitamin D receptor 3' untranslated region genotype in all populations, This f inding may explain contradictory results from recent association studi es using the BsmI marker.