Association of carotid atherosclerosis with genetic polymorphisms of the klotho gene in patients with hypertension

Ryosuke Oguro, Kei Kamide, Yoshihiro Kokubo, Izumi Shimaoka, Ada Congrains, Takeshi Horio, Hironori Hanada, Mitsuru Ohishi, Tomohiro Katsuya, Tomonori Okamura, Toshiyuki Miyata, Yuhei Kawano, Hiromi Rakugi

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Aim: Previous studies suggest that klotho gene polymorphisms may be associated with atherosclerosis, but did not assess the relationship between klotho gene polymorphisms and atherosclerosis parameters such as carotid artery intima-media thickness (IMT). Here, we studied whether klotho single nucleotide polymorphisms (SNP) were associated with carotid atherosclerosis. Methods: All subjects were Japanese. Eight-hundred and fifty-three patients with hypertension (465 men and 388 women) in the outpatient clinic and 1783 subjects from the general population (821 men and 962 women) attending health check-ups were analyzed in the present study. We measured mean IMT of the common carotid artery to evaluate carotid atherosclerosis. Four single nucleotide polymorphisms (SNP) (rs7323281; intron1, rs5644481; exon4, rs3752472; exon3, rs650439; intron4) of klotho were selected as representative SNP in haplotype blocks. Results: Multivariate logistic regression analysis adjusted by confounding factors showed a significant association of rs650439 with carotid atherosclerosis in hypertensive patients (TT vs TA vs AA, P < 0.01; TT + TA vs AA, P < 0.01). By ancova considering confounding factors, rs650439 was also significantly associated with mean IMT (TT + TA vs AA, P = 0.04) in the hypertensive population. However, there was no significant association between klotho SNP and carotid IMT in the general population. Compared to the general population, the subject group with hypertensive patients clearly had more atherosclerosis risk factors. Conclusion: Only in hypertensive patients was klotho rs650439 strongly associated with mean IMT thickening of the common carotid artery. Therefore, klotho SNP (rs650439) may influence on the progression of carotid atherosclerosis in patients with hypertension.

Original languageEnglish
Pages (from-to)311-318
Number of pages8
JournalGeriatrics and Gerontology International
Volume10
Issue number4
DOIs
Publication statusPublished - 2010 Oct
Externally publishedYes

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Carotid Artery Diseases
Genetic Polymorphisms
hypertension
Single Nucleotide Polymorphism
Hypertension
Atherosclerosis
Carotid Intima-Media Thickness
Genes
Common Carotid Artery
Population
outpatient clinic
Women's Health
Ambulatory Care Facilities
Carotid Arteries
Population Groups
Haplotypes
regression analysis
Logistic Models
logistics
Regression Analysis

Keywords

  • Carotid atherosclerosis
  • Klotho
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Gerontology
  • Health(social science)

Cite this

Association of carotid atherosclerosis with genetic polymorphisms of the klotho gene in patients with hypertension. / Oguro, Ryosuke; Kamide, Kei; Kokubo, Yoshihiro; Shimaoka, Izumi; Congrains, Ada; Horio, Takeshi; Hanada, Hironori; Ohishi, Mitsuru; Katsuya, Tomohiro; Okamura, Tomonori; Miyata, Toshiyuki; Kawano, Yuhei; Rakugi, Hiromi.

In: Geriatrics and Gerontology International, Vol. 10, No. 4, 10.2010, p. 311-318.

Research output: Contribution to journalArticle

Oguro, R, Kamide, K, Kokubo, Y, Shimaoka, I, Congrains, A, Horio, T, Hanada, H, Ohishi, M, Katsuya, T, Okamura, T, Miyata, T, Kawano, Y & Rakugi, H 2010, 'Association of carotid atherosclerosis with genetic polymorphisms of the klotho gene in patients with hypertension', Geriatrics and Gerontology International, vol. 10, no. 4, pp. 311-318. https://doi.org/10.1111/j.1447-0594.2010.00612.x
Oguro, Ryosuke ; Kamide, Kei ; Kokubo, Yoshihiro ; Shimaoka, Izumi ; Congrains, Ada ; Horio, Takeshi ; Hanada, Hironori ; Ohishi, Mitsuru ; Katsuya, Tomohiro ; Okamura, Tomonori ; Miyata, Toshiyuki ; Kawano, Yuhei ; Rakugi, Hiromi. / Association of carotid atherosclerosis with genetic polymorphisms of the klotho gene in patients with hypertension. In: Geriatrics and Gerontology International. 2010 ; Vol. 10, No. 4. pp. 311-318.
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AU - Oguro, Ryosuke

AU - Kamide, Kei

AU - Kokubo, Yoshihiro

AU - Shimaoka, Izumi

AU - Congrains, Ada

AU - Horio, Takeshi

AU - Hanada, Hironori

AU - Ohishi, Mitsuru

AU - Katsuya, Tomohiro

AU - Okamura, Tomonori

AU - Miyata, Toshiyuki

AU - Kawano, Yuhei

AU - Rakugi, Hiromi

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N2 - Aim: Previous studies suggest that klotho gene polymorphisms may be associated with atherosclerosis, but did not assess the relationship between klotho gene polymorphisms and atherosclerosis parameters such as carotid artery intima-media thickness (IMT). Here, we studied whether klotho single nucleotide polymorphisms (SNP) were associated with carotid atherosclerosis. Methods: All subjects were Japanese. Eight-hundred and fifty-three patients with hypertension (465 men and 388 women) in the outpatient clinic and 1783 subjects from the general population (821 men and 962 women) attending health check-ups were analyzed in the present study. We measured mean IMT of the common carotid artery to evaluate carotid atherosclerosis. Four single nucleotide polymorphisms (SNP) (rs7323281; intron1, rs5644481; exon4, rs3752472; exon3, rs650439; intron4) of klotho were selected as representative SNP in haplotype blocks. Results: Multivariate logistic regression analysis adjusted by confounding factors showed a significant association of rs650439 with carotid atherosclerosis in hypertensive patients (TT vs TA vs AA, P < 0.01; TT + TA vs AA, P < 0.01). By ancova considering confounding factors, rs650439 was also significantly associated with mean IMT (TT + TA vs AA, P = 0.04) in the hypertensive population. However, there was no significant association between klotho SNP and carotid IMT in the general population. Compared to the general population, the subject group with hypertensive patients clearly had more atherosclerosis risk factors. Conclusion: Only in hypertensive patients was klotho rs650439 strongly associated with mean IMT thickening of the common carotid artery. Therefore, klotho SNP (rs650439) may influence on the progression of carotid atherosclerosis in patients with hypertension.

AB - Aim: Previous studies suggest that klotho gene polymorphisms may be associated with atherosclerosis, but did not assess the relationship between klotho gene polymorphisms and atherosclerosis parameters such as carotid artery intima-media thickness (IMT). Here, we studied whether klotho single nucleotide polymorphisms (SNP) were associated with carotid atherosclerosis. Methods: All subjects were Japanese. Eight-hundred and fifty-three patients with hypertension (465 men and 388 women) in the outpatient clinic and 1783 subjects from the general population (821 men and 962 women) attending health check-ups were analyzed in the present study. We measured mean IMT of the common carotid artery to evaluate carotid atherosclerosis. Four single nucleotide polymorphisms (SNP) (rs7323281; intron1, rs5644481; exon4, rs3752472; exon3, rs650439; intron4) of klotho were selected as representative SNP in haplotype blocks. Results: Multivariate logistic regression analysis adjusted by confounding factors showed a significant association of rs650439 with carotid atherosclerosis in hypertensive patients (TT vs TA vs AA, P < 0.01; TT + TA vs AA, P < 0.01). By ancova considering confounding factors, rs650439 was also significantly associated with mean IMT (TT + TA vs AA, P = 0.04) in the hypertensive population. However, there was no significant association between klotho SNP and carotid IMT in the general population. Compared to the general population, the subject group with hypertensive patients clearly had more atherosclerosis risk factors. Conclusion: Only in hypertensive patients was klotho rs650439 strongly associated with mean IMT thickening of the common carotid artery. Therefore, klotho SNP (rs650439) may influence on the progression of carotid atherosclerosis in patients with hypertension.

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KW - Single nucleotide polymorphism

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