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

- Genetic variants in genes encoding leukotrienes are associated with atherosclerosis.
- Leukotriene haplotype (HapE) significantly interacts with diet on IMT in Caucasians.
- American Indians may have distinct genetic background and dietary habits.
- We confirmed HapE-diet interaction on carotid artery hypertrophy in American Indians.

AbstarctObjectiveGene × 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.MethodsThis 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.ResultsThere 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 (PHapE×n3 = 0.018, PHapE×n6 = 0.040) and vascular mass (PHapE×n3 = 0.012, PHapE×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.ConclusionDietary 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.