Abstract 2300: Association of Carotid Atherosclerosis With Genetic Polymorphisms of Klotho Gene in Patients With Hypertension and in the General Population
Background:Mice deficient in klotho expression exhibit a syndrome resembling premature human aging, especially characterized by advanced atherosclerosis. Previous studies have suggested the significant association of single-nucleotide polymorphisms (SNPs) in the klotho with coronary artery disease in Asian populations.
Aim: Our previous studies suggest that klotho protein plays a protective role in the pathogenesis of atherosclerosis. Present study investigates the relationship between SNPs in klotho and carotid intima-media thickening (IMT) as a phenotype of human atherosclerosis in a Japanese population.
Methods: We have recruited to this study, 853 hypertensive patients and 1783 general populations with written informed consent for genetic analysis. We measured mean-IMT to assess carotid atherosclerosis which was defined as mean-IMT ≥ 1.1 mm. We genotyped SNPs (rs7323281;intron1, rs5644481;exon4, rs3752472;exon3, rs650439;intron4) selected as representative SNPs of haplotype blocks obtained by direct sequencing.
Results: In hypertensive patients, χ2 analysis revealed that rs3752472 (CC+TC vs. TT: P=0.036), and rs650439 (TT vs. TA vs. AA: p=0.024, TT+TA vs. AA: p=0.012) were associated with IMT. Multivariate logistic regression analysis performed after adjusting for confounding factors showed a significant association of rs650439 with carotid atherosclerosis in hypertensive patients ( TT vs. TA vs. AA: P=0.0061, TT+TA vs. AA: P=0.0040). On analysis of covariance (ANCOVA), rs650439 was significantly associated with IMT (TT+TA vs. AA: P=0.045). Furthermore, we have examined the association of rs650439 with IMT in general populations. The multiple logistic analysis after confounding factors revealed that rs650439 has a significant association with progression of IMT (TT vs. TA vs. AA: P=0.042, TT+TA vs. AA: P=0.032).
Conclusion: Taken together the results from genetic analysis using two different subjects, rs650439 in klotho might be playing an important role in the progression of IMT in common carotid artery. We conclude that a SNP of klotho (rs650439) may be associated with advanced IMT in Japanese population.