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(Hypertension. 2000;35:699.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Lys¹⁷³Arg and -344T/C Variants of CYP11B2 in Japanese Patients With Low-Renin Hypertension

Ichiro Komiya; Takashi Yamada; Masaki Takara; Takayuki Asawa; Michio Shimabukuro; Takeshi Nishimori; Nobuyuki Takasu

From the Second Department of Internal Medicine (I.K., M.T., T.A., M.S., N.T.), University of the Ryukyus School of Medicine, Nishihara, Okinawa, Japan; and Kashiwa City Hospital (T.Y., T.N.), Kashiwa, Chiba, Japan.

Correspondence to Ichiro Komiya, MD, Second Department of Internal Medicine, University of the Ryukyus School of Medicine, 207 Uehara, Nishihara, Okinawa 903-0215, Japan. E-mail cnoguchi{at}2naidomon.naha.okinawa.jp

Abstract—We analyzed the association of 2 biallelic polymorphisms of CYP11B2 (P450c11AS) gene (1 in the Lys¹⁷³Arg of exon 3 and the other in the promoter at position -344T/C) with hypertension in 73 hypertensive patients and 134 normotensive subjects. The association between low-renin hypertension and angiotensin I–converting enzyme (ACE) gene was also analyzed. An elevated ratio of plasma aldosterone concentration to plasma renin activity was used to identify low-renin hypertension. Genotypes for CYP11B2 and ACE were determined through polymerase chain reactions. The Arg¹⁷³ allele frequency did not differ between hypertensive patients considered as 1 group (34%) and normotensive control subjects (37%). However, only 22% of 58 CYP11B2 alleles studied in 29 patients with low-renin hypertension were Arg¹⁷³ alleles, whereas the frequency of this allele was 41% in patients with normal- or high-renin hypertension (P=0.033). An analysis of the distribution of -344C and Arg¹⁷³ genotypes indicated that these 2 variants were in complete linkage disequilibrium: -344C was present in a subset of chromosomes carrying the Arg¹⁷³ (P<0.001 in low-renin hypertension). Therefore, the frequency of the -344C allele was low in the patients with low-renin hypertension compared with those with normal- or high-renin hypertension. Deletion (D) allele frequencies of the ACE gene were 31% in the patients with low-renin hypertension, 39% in the patients with normal- or high-renin hypertension, and 29% in normotensive control subjects. We detected an association between the CYP11B2 gene polymorphisms and low-renin hypertension with inappropriate elevation of aldosterone. The decreased frequencies of the Arg¹⁷³ and -344C variants in the CYP11B2 appear to be genetically linked to low-renin hypertension in the Japanese population studied.

Key Words: hypertension, essential • cytochrome P-450 • polymorphism • aldosterone • renin-angiotensin system

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