KLOTHO allele status and the risk of early-onset occult coronary artery disease
Language: 
English
Abstract: 

We previously identified a functional variant of KLOTHO (termed "KL-VS"), which harbors two amino acid substitutions in complete linkage disequilibrium and is associated with reduced human longevity when in homozygosity. Klotho-deficient mice display extensive arteriosclerosis when fed a normal diet, suggesting a potent genetic predisposition. To determine whether klotho influences atherosclerotic risk in humans, we performed cross-sectional studies to assess the association between the KL-VS allele and occult coronary artery disease (CAD) in two independent samples of apparently healthy siblings of individuals with early-onset (age <60 years) CAD (SIBS-I [N=520] and SIBS-II [N=436]). Occult CAD was defined as the occurrence of a reversible perfusion defect during exercise thallium scintigraphy and/or as an abnormal result of an exercise electrocardiogram (SIBS-I, n=97; SIBS-II, n=56). In SIBS-I, the KL-VS allele conferred a relative odds of 1.90 (95% confidence interval 1.21-2.98) for occult CAD, after adjusting for familial intraclass correlations (P<.005). Logistic regression modeling, incorporating known CAD risk factors, demonstrated that the KL-VS allele is an independent risk factor (P<.019) and that the imposed risk of KL-VS allele status is influenced by modifiable risk factors. Hypertension (P<.022) and increasing high-density lipoprotein cholesterol (HDL-C) levels (P<.022) mask or reduce the risk conferred by the KL-VS allele, respectively, whereas current smoking (P<.004) increases the risk. Remarkably concordant effects of the KL-VS allele and modifying factors on the risk of occult CAD were seen in SIBS-II. These results demonstrate that the KL-VS allele is an independent risk factor for occult CAD in two independent high-risk samples. Modifiable risk factors, including hypertension, smoking status, and HDL-C level, appear to influence the risk imposed by this allele.

Author(s): 
Arking, Dan E.
Becker, Diane M.
Yanek, Lisa R.
Fallin, Daniele
Judge, Daniel P.
Moy, Taryn F.
Becker, Lewis C.
Dietz, Harry C.
Item Type: 
Journal Article
Publication Title: 
American Journal of Human Genetics
Journal Abbreviation: 
Am. J. Hum. Genet.
Publication Date: 
2003-05
Publication Year: 
2003
Pages: 
1154-1161
Volume: 
72
Issue: 
5
ISSN: 
0002-9297
DOI: 
10.1086/375035
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 12669274 PMCID: PMC1180268

Turabian/Chicago Citation

Dan E. Arking, Diane M. Becker, Lisa R. Yanek, Daniele Fallin, Daniel P. Judge, Taryn F. Moy, Lewis C. Becker and Harry C. Dietz. 2003-05. "KLOTHO allele status and the risk of early-onset occult coronary artery disease." American Journal of Human Genetics 72: 5: 1154-1161. 10.1086/375035.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1086/375035 | issn = 0002-9297 | volume = 72 | pages = 1154-1161 | last = Arking | first = Dan E. | coauthors = Becker, Diane M., Yanek, Lisa R., Fallin, Daniele, Judge, Daniel P., Moy, Taryn F., Becker, Lewis C., Dietz, Harry C. | title = KLOTHO allele status and the risk of early-onset occult coronary artery disease | journal = American Journal of Human Genetics | date = 2003-05 | pmid = | pmc = }} </ref>