Estimating Carrier Rates and Prevalence of Porphyria-Associated Gene Variants in the Chinese Population Based on Genetic Databases

Abstract

Abstract Porphyria is a group of rare metabolic disorders caused by mutations in genes that encode crucial enzymes in the heme biosynthetic pathway. However, the lack of comprehensive genetic analysis of porphyria in the Chinese population makes it challenging to identify and diagnose carriers of the condition. Using the ChinaMAP database, we determined the frequencies of P/LP porphyria-associated gene variants according to the ACMG guidelines. We also calculated the carrier rates and prevalence for each type of porphyria in the Chinese population under the Hardy-Weinberg equilibrium (HWE). Compared with the gnomAD database, the genetic spectrum of porphyria-related P/LP variants in the Chinese population is distinct. In the ChinaMAP database, we identified 23 of these variants. We estimated the carrier rates for autosomal dominant porphyria (AIP, HCP, VP, PCT) in the Chinese population to be 1/1059, 1/1513, 1/10588, and 1/1765, respectively. For autosomal recessive porphyria (ADP, EPP, HEP, CEP), we estimated carrier rates of 1/5294, 1/2117, 1/1765, and 1/2647, with predicted prevalence rates of 1/112105744, 1/13312, 1/12456194, and 1/28026436, respectively. Notably, 12 of the variants we identified were unique to the Chinese population. The predicted prevalence rate of EPP is the highest among the various types of porphyria in the Chinese population, while the others are moderate to low. This study is the initial comprehensive genetic research on porphyria in the Chinese population. By outlining the genetic characteristics of various porphyria types among the Chinese, it provides scientifically sound reference data necessary for both research and genetic screening to identify porphyria carriers.