Mutational analysis of the Kir6.1 gene in Chinese hypertensive patients treated with the novel ATP-sensitive potassium channel opener iptakalim.

Iptakalim is a novel K(ATP) opener with antihypertensive properties. The Kir6.1 gene is one of the candidate genes that may influence the response to iptakalim in hypertensive patients. We aimed to ascertain whether a mutation in the coding region of the Kir6.1 gene is present in Chinese Han hypertensive patients. The study population included 162 Chinese Han hypertensive patients (81 men and 81 women with a mean age of 55±9 years). Mutational analysis of the coding region of Kir6.1 was performed using PCR-SSCP and direct sequencing. No missense or nonsense mutations were found in these samples, while a single base pair substitution (C to T) at nucleotide position 111 in exon 2 of the coding region was noted in four patients (one female and three male), who were all heterozygous for the mutation. This C to T substitution did not result in an amino acid substitution (Ile37Ile, silent mutation). In the remaining 158 patients, no mutation was detected. The blood pressure of these four patients carrying the I37I polymorphism was well controlled by iptakalim. No mutation that alters the primary structure of Kir6.1 was detected in Chinese Han hypertensive patients. The results indicate that abnormality in the primary structure of Kir6.1 is not involved in the genetic pathogenesis of essential hypertension in Chinese Han hypertensive patients and has no effect on the BP response to iptakalim treatment.