Analysis of CYP21 coding polymorphisms in three ethnic populations: Further evidence of nonamplifying CYP21 alleles among whites

Background: Adrenal steroid 21-hydroxylase is essential for the synthesis o f both mineralocorticoids and glucocorticoids. The gene for this enzyme, CY P21, contains several frequent coding polymorphisms. Because of its essenti al function in steroid synthesis, polymorphisms in this enzyme might influe nce a variety of disease processes. However, before disease-association stu dies are performed, it is important to understand the frequency of these po lymorphisms among normal individuals. Methods: Using polymerase chain reaction (PCR) with restriction enzyme dige stion or size length polymorphism analysis, we measured the frequencies of the +Leu(10), Arg 102Lys, and Ser268Thr polymorphisms in CYP21 in healthy w hites, blacks, and Indian Americans. The subjects were all young female col lege students participating in a study of relative risks for cardiovascular disease in these populations. Results: The frequency of each polymorphism among whites, blacks, and India n Americans were as follows: +Leu(10), 0.55, 0.96, 0.75; Arg102, 0.63, 0.97 , 0.82; and Ser268, 0.92, 0.68, 0.79, respectively. With the exception of t he frequencies of the Ser268Thr polymorphism among blacks and Indian Americ ans, there were significantly different frequencies of each polymorphism am ong all groups (P < .05). Among whites, the distribution of genotypes for t he +Leu(10) and Arg102Lys polymorphisms deviated significantly from expecte d Hardy-Weinberg values because of an excess of homozygotes. Conclusions: Among the ethnic groups, there are statistically significant d ifferences in the frequencies of these common coding polymorphisms in CYP21 that need to be considered in disease-association studies. Deviation from Hardy-Weinberg distributions might be explained by allelic dropout during P CR, a phenomenon previously reported at this locus.