The genetic factors related to early-onset hypertension are largely unknown. This study aimed to determine the spectrum of steroid metabolism gene variants and the clinical relationships of these variants to phenotypes in Chinese patients with early-onset hypertension. A total of 306 consecutive early-onset hypertensive patients were recruited. All coding exons and flanking intronic regions of KCNJ5, CYP11B1, and CYP17A1 were sequenced. Long-distance polymerase chain reaction was used to search for a CYP11B1/CYP11B2 chimeric gene. Pedigree investigations and genotype-phenotype analyses were performed for patients with rare variants. Nine rare variants were detected in eight patients (2.6%), but no CYP11B1/CYP11B2 chimeric gene was identified. One patient and two of her siblings were found to carry compound heterozygous mutations (C183Y and T390R) in CYP17A1 and were eventually diagnosed with atypical congenital adrenal hyperplasia. Patients with rare variants had younger ages of onset [17 (16, 20) vs. 30 (23, 35) years old, p = 0.010] and higher systolic blood pressure (148.5 ± 9.6 vs. 137.9 ± 17.8 mmHg, p = 0.021) than those without rare variants. Additionally, the patients and their relatives carrying rare variants exhibited increased serum free corticosterone [230.4 (7.4, 533.0) vs. 1.9 (0.9, 6.7)ng/ml, p = 0.001] and 11-deoxycorticosterone [16.16 (0.59, 33.23) vs. 0.77 (0.41, 0.96)ng/ml, p = 0.038] levels. Genetic testing is useful for the etiologic diagnosis of early-onset hypertension. Rare variants in steroid metabolism genes were associated with more severe clinical expression and abnormal circulating steroid metabolites in patients with early-onset hypertension.
Keywords: congenital adrenal hyperplasia; genotype–phenotype correlation; hypertension; rare variant; steroid metabolism.