The A190T variation in human polycystin 2, previously known as a missense mutation, is a nonsynonymous cSNP in Korean population

Polycystin 2 (PKD2) is an ion channel that regulates the intracellular calcium ion concentration. Amino acid changes in PKD2 are known to cause autosomal dominant polycystic kidney disease (ADPKD), and are possibly associated with many other complex diseases. In an effort to find cSNPs (single nucleotide polymorphisms within cDNA sequence) in PKD2, we used direct sequencing analysis to screen the entire coding region of the PKD2 gene. We identified a major nonsynonymous cSNP, Ala 190Thr (A190T), in the N-terminal intracellular domain of PKD2. This nonsynonymous cSNP was previously reported as a mutation for ADPKD. However, this study excluded the possibility that the A190T variation was a missense mutation for ADPKD by a thorough clinical evaluation and population study. In 500 genetically unrelated Koreans, the allele frequencies of G and A at the A190T variation were 64% and 36%, respectively. The genotype frequency of the cSNP was not deviated from Hardy-Weinberg equilibrium. These experimental results indicate that mutational research needs to be confirmed by a thorough clinical evaluation and population study. Furthermore, the A190T variation is implicated as having possible causative roles in the pathogenesis of various ADPKD-related diseases. Intensive population studies should be conducted to address the etiological role of the A190T variation in these ADPKD-related diseases.