Genetic Basis of Variation in Carotid Artery Plaque in the San Antonio Family Heart Study

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Abstract
In contrast to the commonly used quantitative marker of subclinical atherosclerosis, namely intima-media thickness, we investigated the extent to which the presence or absence of carotid artery plaque (CAP) was under genetic control. The study population consisted of 750 individuals distributed across 29 randomly ascertained extended Mexican American pedigrees who participated in the second examination cycle of the San Antonio Family Heart Study. Extracranial focal CAP was identified by B-mode ultrasound bilaterally in the internal carotid artery or the carotid bulb. Using a variance decomposition approach implemented in the SOLAR computer program, we performed genetic analysis on the discrete trait CAP (ie, liability to disease) using a threshold model. Covariates considered in the analysis included age, sex, diabetes, current smoking status, lipid levels, and markers of hypertension and obesity. Fifty-one of 461 women and fifty-seven of 289 men with a mean age of 42.1 years had evidence of a plaque in the right and/or left carotid artery. The age- and sex-adjusted heritability (h(2)+/-SE) for CAP was significant (h(2)=0.28+/-0.15, P=0.01). Furthermore, after adjustment for additional covariates that contributed significantly to the model (P<0.05; diabetes, hypertension, body mass index, waist circumference, and smoking status), heritability remained significant (h(2)=0.23+/-0.15, P=0.03). Our data indicate that after established cardiovascular risk factors are controlled for, the variation of the discrete trait CAP is under appreciable additive genetic influences.