High incidence of hypertension-mediated organ damage in a series of Chinese patients with 17α-hydroxylase deficiency

Abstract Objective To analyze the prevalence of hypertension-mediated organ damage (HMOD) and its relationship with enzyme activity of mutant CYP17A1 and other risk factors in patients with 17α-hydroxylase/17,20-lyase deficiency (17-OHD). Methods A total of 68 patients with 17-OHD were recruited in the Peking Union Medical Hospital from 2003 to 2021.The incidence of hypertension and HMOD was analyzed. CYP17A1 sequencing was performed for all patients and the enzyme activity of CYP17A1 mutant was determined by analyzing the characteristics of mutation itself and the functional data reported previously. A logistic regression model was employed to analyze the factors related to HMOD and the specific damaged organs in patients with 17-OHD. Result(s): Sixty-five patients (95.6%) exhibited hypertension,32 of whom were diagnosed with HMOD in this 17-OHD cohort. c.985_987del TAC ins AA (p. Y329KfsX418) (53.8%) and c.1459_1467del (p. del D487_F489) (11.4%) were the top 2 mutations in this cohort, and no correlation was found between enzyme activity of mutant CYP17A1 and HMOD. Age, hypertension grade, and hypokalemia grade were independent risk factors for HMOD in 17-OHD patients. The risk of HMOD increased by 27% for each additional year of age, 7.7-fold for each one-grade increase in hypertension level, and 1.7-fold for each grade of exacerbation of hypokalemia. Conclusion Patients with 17-OHD experience high incidence of HMOD. There was no correlation between the HMOD occurrence and enzyme activity of mutant CYP17A1 .Age, hypertension grade, and hypokalemia grade are independent risks for the occurrence of HMOD.