Leukotriene haplotype × diet interaction on carotid artery hypertrophy and atherosclerosis in American Indians: the Strong Heart Family Study.

OBJECTIVE: Gene × diet interaction plays an important role in atherosclerosis, an inflammatory disorder. Leukotrienes are the most potent inflammatory mediators, and genetic variants encoding leukotriene genes have been implicated in atherosclerosis. This study tests nutrigenetic interaction of a previously defined leukotriene haplotype on carotid artery hypertrophy and atherosclerosis in American Indians. METHODS: This study included 3402 American Indians participating in the Strong Heart Family Study (SHFS). Carotid artery measurements, including intima-media thickness (IMT), vascular mass, and plaque, were assessed using ultrasound. Eleven tagSNPs in the leukotriene A4 hydrolase (LTA4H) gene were genotyped in all subjects. Main haplotype effect and haplotype × diet interaction were examined by generalized estimating equation, adjusting for known risk factors. RESULTS: There was no significant main effect of haplotype or diet on any of the carotid artery measures. However, a previously defined LTA4H haplotype, called HapE, significantly interacted with dietary intake of n-3 and n-6 fatty acids on both IMT (P(HapE × n3) = 0.018, P(HapE × n6) = 0.040) and vascular mass (P(HapE × n3) = 0.012, P(HapE × n6) = 0.018), but not plaque. The direction of this nutrigenetic interaction on IMT was consistent with that reported in a recent study of Caucasian twins. CONCLUSION: Dietary intake of polyunsaturated fatty acids significantly modifies the effect of a leukotriene haplotype on carotid artery hypertrophy but not atherosclerosis in American Indians, independent of established cardiovascular risk factors. Replication of nutrigenetic interaction in two distinct ethnic groups suggests the robustness and generalizability of our findings to diverse populations.

Prevalence and correlates of subclinical atherosclerosis in Alaska Eskimos: the GOCADAN study.

BACKGROUND AND PURPOSE: The recent increase in clinical cardiovascular disease in Alaska Eskimos suggests that changes in traditional lifestyle may have adverse public health consequences. This study examines the prevalence of subclinical vascular disease and its relation to risk factors in Alaska Eskimos. METHODS: Participants in the population-based Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) Study underwent evaluation of cardiovascular disease risk factors and carotid ultrasound. Outcome variables were carotid intimal-medial thickness and presence and extent of atherosclerosis. RESULTS: In multivariate analyses, intimal-medial thickness and presence and extent of atherosclerosis were all associated with traditional cardiovascular disease risk factors but not dietary intake of omega-3 fatty acids. Rates of carotid atherosclerosis were higher than those reported in 2 large population-based US studies. CONCLUSIONS: Alaska Eskimos have similar traditional risk factors for carotid atherosclerosis as other ethnic and racial populations but have higher prevalences of atherosclerosis, possibly attributable to higher rates of smoking.

Consumption of omega-3 fatty acids is not associated with a reduction in carotid atherosclerosis: the Genetics of Coronary Artery Disease in Alaska Natives study.

OBJECTIVE: This study was designed to evaluate the relation between omega-3 fatty acid (FA) consumption and atherosclerosis. BACKGROUND: The hypothesis that omega-3 FAs protect against atherosclerosis has not been tested with objective measures of atherosclerosis. METHODS: A population-based sample of 1131 Alaskan Eskimos of age >or=18 underwent ultrasound assessment of carotid atherosclerosis. Those of age >35 (N=686) were included in the analysis. Diet was assessed by a food frequency questionnaire. Intimal-medial thickness (IMT) of the far wall of the distal common carotid arteries and plaque score (number of segments containing plaque) were assessed. RESULTS: Mean consumption of total omega-3 FAs was 4.76 g/day in those without and 5.07 g/day in those with plaque. In models adjusting for relevant risk factors, presence and extent of plaque were unrelated to intake of C20-22 omega-3 FAs or total omega-3 FAs. In contrast, the odds of plaque rose significantly with quartiles of palmitic (p=0.02) and stearic acid intake (p=0.04). The extent of plaque (or plaque score) was also associated with a higher percentage intake of palmitic acid (p=0.01). IMT was negatively associated with grams of C20-22 omega-3 FAs (p=0.05), total omega-3 (p=0.05), palmitate (p=0.03), and stearate (p=0.03) consumed. CONCLUSIONS: Dietary intake of omega-3 FAs in a moderate-to-high range does not appear to be associated with reduced plaque, but is negatively associated with IMT. The presence and extent of carotid atherosclerosis among Eskimos is higher with increasing consumption of saturated FAs.