title: Leukotriene haplotype × diet interaction on carotid artery hypertrophy and atherosclerosis in American Indians: the Strong Heart Family Study.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA. Electronic address: jzhao5@tulane.edu.
authors: Jinying
authors: J
authors: Zhao
authors: Weill Cornell Medical College, New York, NY, USA.
authors: Mary J
authors: MJ
authors: Roman
authors: Weill Cornell Medical College, New York, NY, USA.
authors: Richard B
authors: RB
authors: Devereux
authors: Center for American Indian Health Research, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors: Fawn
authors: F
authors: Yeh
authors: Center for American Indian Health Research, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors: Ying
authors: Y
authors: Zhang
authors: Texas Biomedical Research Institute, San Antonio, TX, USA.
authors: Karin
authors: K
authors: Haack
authors: Missouri Breaks Industries Research Inc, Timber Lake, SD, USA.
authors: Lyle G
authors: LG
authors: Best
authors: Texas Biomedical Research Institute, San Antonio, TX, USA.
authors: Shelley A
authors: SA
authors: Cole
authors: Center for American Indian Health Research, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors: Elisa T
authors: ET
authors: Lee
authors: MedStar Health Research Institute Hyattsville, MD and Georgetown and Howard Universities Centers for Translational Sciences, Washington, DC, USA.
authors: Barbara V
authors: BV
authors: Howard
mesh_terms: D000328:Adult; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000473:pathology*; D002340:Carotid Artery Diseases / Q000209:etiology / Q000473:pathology; D059168:Carotid Intima-Media Thickness; D004041:Dietary Fats / Q000008:administration & dosage*; D004851:Epoxide Hydrolases / Q000235:genetics*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage; D043371:Fatty Acids, Omega-6 / Q000008:administration & dosage; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006984:Hypertrophy / Q000473:pathology; D007198:Indians, North American / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D004041:Dietary Fats; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D004851:Epoxide Hydrolases; C043134:leukotriene A4 hydrolase
keywords: American Indians; Carotid atherosclerosis; Gene–diet interaction; Leukotriene haplotype