Alpha-adducin Gly460Trp polymorphism is associated with low renin hypertension in younger subjects in the Ohasama study

Background The Gly460Trp polymorphism of the alpha-adducin gene (ADD-1) has been examined as a candidate gene for essential hypertension with salt sensitivity in the Caucasian population. However, we failed to detect a positive association between the Gly460Trp polymorphism of ADD-1 and hypertension in a small series of Japanese subjects. Objective To examine the precise association between the Gly460Trp polymorphism of ADD-1 and blood pressure (BP), we carried out an association study using a Japanese population: the Ohasama Study. Design Subjects (n = 1490) were recruited from participants in the Ohasama Study, which is a cohort in a rural community of northern Japan. Methods DNA was extracted from the buffy coat of the participants who gave informed consent for genetic analysis, and the Gly460Trp polymorphism of ADD-1 was determined by the TaqMan polymerase chain reaction method. Various BP values (casual BP, ambulatory BP and home BP) were measured in the Ohasama study. We used the mean values of these BP measurements for analysis. Results The frequencies of genotypes in the Ohasama population were 23% Gly/Gly, 49% Gly/Trp, and 28% Trp/Trp. In the baseline characteristics, age, sex, body mass index, frequency of diabetes and hyperlipidemia were significantly different between hypertensive or normotensive subjects. In total subjects, all BP values were not different among ADD-1 genotypes. In the younger subjects (< 60 years old) with low plasma renin activity (< 1.0 ng/ml per h), however, ambulatory BP and home BP were significantly higher in the subjects with the Gly/Trp or Trp/Trp genotypes of ADD-1 polymorphism than in those with the Gly/Gly genotype. In the same population, the frequency of the Gly/Trp or Trp/Trp genotypes of ADD-1 was significantly higher in hypertensives than in normotensives (83 versus 72%, χ12 = 4.04, P < 0.05; odds ratio, 2.12; 95% confidence interval, 1.02–4.68). Conclusions These findings suggest the possibility that the Gly460Trp polymorphism of ADD-1 is associated with low renin hypertension.

[1]  D. J. Patel,et al.  The Elastic Symmetry of Arterial Segments in Dogs , 1969, Circulation research.

[2]  T. G. Coleman,et al.  Quantitative analysis of the pathophysiology of hypertension. , 1969, Circulation research.

[3]  G. Bianchi,et al.  Renal function of isolated perfused kidneys from hypertensive (MHS) and normotensive (MNS) rats of the Milan strain: role of calcium. , 1987, Journal of hypertension.

[4]  R. Schmieder,et al.  Ambulatory blood pressure monitoring: practical considerations. , 1988, American heart journal.

[5]  Y. Imai,et al.  Clinical evaluation of semiautomatic and automatic devices for home blood pressure measurement: comparison between cuff-oscillometric and microphone methods , 1989, Journal of hypertension.

[6]  A. Guyton,et al.  The Surprising Kidney‐Fluid Mechanism for Pressure Control ‐Its Infinite Gain! , 1990, Hypertension.

[7]  G. Borsani,et al.  Molecular cloning of an adducin-like protein: evidence of a polymorphism in the normotensive and hypertensive rats of the Milan strain. , 1991, Biochemical and Biophysical Research Communications - BBRC.

[8]  P. Ferrari,et al.  Sodium transport kinetics in erythrocytes and inside-out vesicles from Milan rats. , 1991, Journal of hypertension.

[9]  P. Ferrari,et al.  Na+/K+/Cl- cotransport in resealed ghosts from erythrocytes of the Milan hypertensive rats. , 1992, Biochimica et biophysica acta.

[10]  C. Hughes,et al.  Adducin: a Physical Model with Implications for Function in Assembly of Spectrin-Actin Complexes (*) , 1995, The Journal of Biological Chemistry.

[11]  F. Valtorta,et al.  Hypertension-associated point mutations in the adducin alpha and beta subunits affect actin cytoskeleton and ion transport. , 1996, The Journal of clinical investigation.

[12]  Cristina Barlassina,et al.  Polymorphisms of α-adducin and salt sensitivity in patients with essential hypertension , 1997, The Lancet.

[13]  Detection.  The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) , 1997 .

[14]  Shigeru Hisamichi,et al.  Home blood pressure measurement has a stronger predictive power for mortality than does screening blood pressure measurement: a population‐based observation in Ohasama, Japan , 1998, Journal of hypertension.

[15]  T. Ogihara,et al.  No association between alpha-adducin 460 polymorphism and essential hypertension in a Japanese population. , 1998, American journal of hypertension.

[16]  N. Iwai,et al.  Polymorphism of alpha-adducin in Japanese patients with essential hypertension. , 1998, Hypertension research : official journal of the Japanese Society of Hypertension.

[17]  N. Glorioso,et al.  The role of alpha-adducin polymorphism in blood pressure and sodium handling regulation may not be excluded by a negative association study. , 1999, Hypertension.

[18]  E. Boerwinkle,et al.  Association and linkage analysis of the α-adducin gene and blood pressure , 2000 .

[19]  N. Samani,et al.  Alpha-adducin polymorphism in hypertensives of South African ancestry. , 2000, American journal of hypertension.

[20]  L. Groop,et al.  Role of the Gly460Trp polymorphism of the α-adducin gene in primary hypertension in Scandinavians , 2000, Journal of Human Hypertension.

[21]  R. Olshen,et al.  Lack of evidence for an association between alpha-adducin and blood pressure regulation in Asian populations. , 2000, American journal of hypertension.

[22]  E. Boerwinkle,et al.  Association and linkage analysis of the alpha-adducin gene and blood pressure. , 2000, American journal of hypertension.

[23]  F. Rosendaal,et al.  Association of the alpha-adducin polymorphism with blood pressure and risk of myocardial infarction. , 2000, Journal of human hypertension.

[24]  S. Hunt,et al.  Low-Renin Hypertension, Altered Sodium Homeostasis, and an &agr;-Adducin Polymorphism , 2002, Hypertension.