| Summary: | <p>Abstract</p> <p>Background</p> <p>Vascular disease is a feature of aging, and coronary vascular events are a major source of morbidity and mortality in rare premature aging syndromes. One such syndrome is caused by mutations in the lamin A/C (<it>LMNA</it>) gene, which also has been implicated in familial insulin resistance. A second gene related to premature aging in man and in murine models is the <it>KLOTHO </it>gene, a hypomorphic variant of which (KL-VS) is significantly more common in the first-degree relatives of patients with premature coronary artery disease (CAD). We evaluated whether common variants at the <it>LMNA </it>or <it>KLOTHO </it>genes are associated with rigorously defined premature CAD.</p> <p>Methods</p> <p>We identified 295 patients presenting with premature acute coronary syndromes confirmed by angiography. A control group of 145 patients with no evidence of CAD was recruited from outpatient referral clinics. Comprehensive haplotyping of the entire <it>LMNA </it>gene, including the promoter and untranslated regions, was performed using a combination of TaqMan<sup>® </sup>probes and direct sequencing of 14 haplotype-tagging single nucleotide polymorphisms (SNPs). The KL-VS variant of the <it>KLOTHO </it>gene was typed using restriction digest of a PCR amplicon.</p> <p>Results</p> <p>Two SNPs that were not in Hardy Weinberg equilibrium were excluded from analysis. We observed no significant differences in allele, genotype or haplotype frequencies at the <it>LMNA </it>or <it>KLOTHO </it>loci between the two groups. In addition, there was no evidence of excess homozygosity at the <it>LMNA </it>locus.</p> <p>Conclusion</p> <p>Our data do not support the hypothesis that premature CAD is associated with common variants in the progeroid syndrome genes LMNA and KLOTHO.</p>
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