Heritability of carotid artery intima-medial thickness in type 2 diabetes.
OBJECTIVE
Carotid artery intima-medial thickness (IMT), a marker of subclinical atherosclerosis, is a strong predictor of subsequent cardiovascular morbidity. The role of genetic factors in thickening of the carotid wall remains largely unknown. We hypothesize that in families with multiple members having diabetes, carotid IMT is likely to be associated with both inherited and environmental factors.


METHODS
To determine the extent of the familial aggregation of carotid IMT in the presence of type 2 diabetes, we studied 252 individuals with type 2 diabetes (mean age 60.6 years) from 122 families. Common carotid artery IMT was measured by high-resolution B-mode ultrasonography. Other measured factors included lipid levels, body mass index, fasting glucose, hemoglobin A1c, albumin/creatinine ratio, and self-reported medical history. Heritability estimates were obtained by using variance component methodology, as implemented in the SOLAR software package. Tests for association between carotid IMT and variables were performed by using mixed model analysis while accounting for the correlation due to family structure.


RESULTS
The age-, sex-, and race-adjusted heritability estimate for carotid IMT was 0.32 (SE 0.17, P=0.02). Further adjustment for total cholesterol, hypertension status, and current smoking status resulted in a heritability estimate of 0.41 (SE 0.16, P=0.004). The strongest predictors of carotid IMT, after adjusting for age and sex, were ethnicity (African American versus white), total cholesterol, and smoking status.


CONCLUSIONS
These data provide empirical evidence that subclinical cardiovascular disease has a significant genetic component and merits a search for the genes involved in susceptibility to the atherosclerotic complications of diabetes.
Lange
Leslie A
LA
Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Bowden
Donald W
DW
Langefeld
Carl D
CD
Wagenknecht
Lynne E
LE
Carr
J Jeffrey
JJ
Rich
Stephen S
SS
Riley
Ward A
WA
Freedman
Barry I
BI
D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D044383:Black People / Q000235:genetics; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000235:genetics*; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging; D015897:Comorbidity; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009657:North Carolina / Q000453:epidemiology; D010375:Pedigree; D012307:Risk Factors; D017678:Sex Distribution; D017539:Tunica Intima / Q000000981:diagnostic imaging*; D017540:Tunica Media / Q000000981:diagnostic imaging*; D014463:Ultrasonography; D044465:White People / Q000235:genetics; D001741:Black or African American