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

MedStar author(s):
Citation: Atherosclerosis. 233(1):165-71, 2014 Mar.PMID: 24529139Institution: MedStar Health Research InstituteForm of publication: Journal ArticleMedline article type(s): Journal Article | Research Support, N.I.H., ExtramuralSubject headings: *Carotid Arteries/pa [Pathology] | *Dietary Fats/ad [Administration & Dosage] | *Epoxide Hydrolases/ge [Genetics] | *Indians, North American/ge [Genetics] | Adult | Carotid Arteries/us [Ultrasonography] | Carotid Artery Diseases/et [Etiology] | Carotid Artery Diseases/pa [Pathology] | Carotid Intima-Media Thickness | Fatty Acids, Omega-3/ad [Administration & Dosage] | Fatty Acids, Omega-6/ad [Administration & Dosage] | Female | Genotype | Haplotypes | Humans | Hypertrophy/pa [Pathology] | Male | Middle Aged | Polymorphism, Single NucleotideISSN:
  • 0021-9150
Name of journal: AtherosclerosisAbstract: 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. Copyright 2014 Elsevier Ireland Ltd. All rights reserved.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 x diet interaction were examined by generalized estimating equation, adjusting for known risk factors.OBJECTIVE: Gene x 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.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 x n3) = 0.018, P(HapE x n6) = 0.040) and vascular mass (P(HapE x n3) = 0.012, P(HapE x 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.All authors: Best LG, Cole SA, Devereux RB, Haack K, Howard BV, Lee ET, Roman MJ, Yeh F, Zhang Y, Zhao JDigital Object Identifier: Date added to catalog: 2014-11-11
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Journal Article MedStar Authors Catalog Article Available 24529139

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. Copyright 2014 Elsevier Ireland Ltd. All rights reserved.

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 x diet interaction were examined by generalized estimating equation, adjusting for known risk factors.

OBJECTIVE: Gene x 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.

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 x n3) = 0.018, P(HapE x n6) = 0.040) and vascular mass (P(HapE x n3) = 0.012, P(HapE x 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.

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