Association of Genetic Polymorphisms of Sodium-Calcium Exchanger 1 Gene, NCX1, with Hypertension in a Japanese General Population
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<B>The Na<SUP>+</SUP>/Ca<SUP>2+</SUP> exchanger (NCX) is a membrane protein involved in calcium homeostasis, catalyzing the exchange of one Ca<SUP>2+</SUP> ion for three Na<SUP>+</SUP> ions across the cell membrane. The Na<SUP>+</SUP>/Ca<SUP>2+</SUP> exchange has been suggested to play a role in the pathogenesis of hypertension. Therefore, we examined whether genetic variations in <I>NCX1</I> were associated with hypertension. Among 15 polymorphisms identified in 96 hypertensive subjects by sequencing the entire exon and promoter regions of <I>NCX1</I>, 7 representative polymorphisms with a minor allele frequency of greater than 4% were genotyped in 1,865 individuals, of whom 787 were hypertensive and 1,072 were normotensive. These subjects were residents of Suita City and were randomly selected as a population for the Suita cohort study. Multivariate logistic regression analysis performed after adjusting for age, body mass index, hyperlipidemia, diabetes mellitus, smoking, and drinking revealed that the -23200T>C and -23181T>C polymorphisms in the 5′ upstream region of exon 1c were significantly associated with hypertension in men (-23200T>C: CC <I>vs.</I> TC+TT: odds ratio=0.61; 95% confidence intervals: 0.39 to 0.97; <I>p</I> =0.04) and in women (-23181T>C: CC <I>vs.</I> TC+TT: odds ratio=1.45; 95% confidence intervals: 1.04 to 2.02; <I>p</I> =0.03), respectively. Thus, our study suggests that <I>NCX1</I> is one of the genes related to susceptibility to essential hypertension in the Japanese general population. (<I>Hypertens Res</I> 2004; 27: 697-702)</B>
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