Candidate gene analysis in premature pubarche and adolescent hyperandrogenism

Objective: To identify genetic markers associated with premature pubarche i n children and hyperandrogenism in adolescent girls. Design: Association study. Setting: Academic research environment. Patient(s): Forty children with premature pubarche (PP), 29 adolescent girl s with hyperandrogenism (HA), and 15 healthy control women. Intervention(s): None. Main Outcome Measure(s): Genetic variations at five loci selected because o f known associations with hyperandrogenism, insulin resistance, hyperinsuli nemia, or obesity. Result(s): Heterozygosity for CYP21 mutations was identified in 14 of 40 (3 5%) PP, 8 of 29 (28%) HA, and 1 of 30 (3%) controls. Heterozygosity for HSD 3B2 variants was identified in 3 of 40 (7.5%) PP, 5 of 29 (17%) HA, and 0/1 5 controls. Among the PP, 11 of 80 (14%), 5 of 80 (6%), and 7 of 80 (9%) al leles showed the IRS-1, GRL, and ADRB3 variants, respectively. Among the HA , 5 of 58 (8.6%), 3 of 58 (58), and 6 of 58 (10%) alleles showed the IRS-1, GRL, and ADRB3 variants, respectively. Among the control participants, var iant allele frequency was 1 of 30 (3.3%) for IRS-1, 2 of 30 (6.6%) for GRL, and 2 of 30 (6.6%) for ADRB3. Conclusion(s): Our findings suggest that the development of PP and HA can b e associated with the occurrence of multiple sequence variants at five susc eptibility loci, especially steroidogenic enzyme genes. This approach offer s a novel paradigm to investigate and identify the genetic factors relevant to polycystic ovary syndrome. (C) 2001 by American Society for Reproductiv e Medicine.