• Ryosuke Oguro, Kei Kamide, Yoshihiro Kokubo, Izumi Shimaoka, Ada Congrains, Takeshi Horio, Hironori Hanada, Mitsuru Ohishi, Tomohiro Katsuya, Tomonori Okamura, Toshiyuki Miyata, Yuhei Kawano, and Hiromi Rakugi.
• Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.
• Geriatr Gerontol Int. 2010 Oct 1; 10 (4): 311-8.

AimPrevious 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.MethodsAll 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.ResultsMultivariate 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.ConclusionOnly 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.© 2010 Japan Geriatrics Society.

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