title: Genetic variation in the raptor gene is associated with overweight but not hypertension in American men of Japanese ancestry.
abstract: BACKGROUND
  The mechanistic target of rapamycin (mTOR) pathway is pivotal for cell growth. Regulatory associated protein of mTOR complex I (Raptor) is a unique component of this pro-growth complex. The present study tested whether variation across the raptor gene (RPTOR) is associated with overweight and hypertension.
  
  
  METHODS
  We tested 61 common (allele frequency ≥ 0.1) tagging single nucleotide polymorphisms (SNPs) that captured most of the genetic variation across RPTOR in 374 subjects of normal lifespan and 439 subjects with a lifespan exceeding 95 years for association with overweight/obesity, essential hypertension, and isolated systolic hypertension. Subjects were drawn from the Honolulu Heart Program, a homogeneous population of American men of Japanese ancestry, well characterized for phenotypes relevant to conditions of aging. Hypertension status was ascertained when subjects were 45-68 years old. Statistical evaluation involved contingency table analysis, logistic regression, and the powerful method of recursive partitioning.
  
  
  RESULTS
  After analysis of RPTOR genotypes by each statistical approach, we found no significant association between genetic variation in RPTOR and either essential hypertension or isolated systolic hypertension. Models generated by recursive partitioning analysis showed that RPTOR SNPs significantly enhanced the ability of the model to accurately assign individuals to either the overweight/obese or the non-overweight/obese groups (P = 0.008 by 1-tailed Z test).
  
  
  CONCLUSIONS
  Common genetic variation in RPTOR is associated with overweight/obesity but does not discernibly contribute to either essential hypertension or isolated systolic hypertension in the population studied.
authors.affiliation: brian.morris@sydney.edu.au.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Morris
authors.affiliation: University of Oklahoma Health Sciences Center, Reynolds Department of Geriatric Medicine, Oklahoma City, Oklahoma;
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Carnes
authors.affiliation: Honolulu Heart Program (HHP)/Honolulu-Asia Aging Study (HAAS), Department of Research, Kuakini Medical Center, Honolulu, Hawaii;
authors.forename: Randi
authors.initials: R
authors.lastname: Chen
authors.affiliation: Honolulu Heart Program (HHP)/Honolulu-Asia Aging Study (HAAS), Department of Research, Kuakini Medical Center, Honolulu, Hawaii;
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Donlon
authors.affiliation: Honolulu Heart Program (HHP)/Honolulu-Asia Aging Study (HAAS), Department of Research, Kuakini Medical Center, Honolulu, Hawaii;
authors.forename: Qimei
authors.initials: Q
authors.lastname: He
authors.affiliation: Honolulu Heart Program (HHP)/Honolulu-Asia Aging Study (HAAS), Department of Research, Kuakini Medical Center, Honolulu, Hawaii; Public Health Sciences, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii;
authors.forename: John S
authors.initials: JS
authors.lastname: Grove
authors.affiliation: Honolulu Heart Program (HHP)/Honolulu-Asia Aging Study (HAAS), Department of Research, Kuakini Medical Center, Honolulu, Hawaii; Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii;
authors.forename: Kamal H
authors.initials: KH
authors.lastname: Masaki
authors.affiliation: Honolulu Heart Program (HHP)/Honolulu-Asia Aging Study (HAAS), Department of Research, Kuakini Medical Center, Honolulu, Hawaii;
authors.forename: Ayako
authors.initials: A
authors.lastname: Elliott
authors.affiliation: Honolulu Heart Program (HHP)/Honolulu-Asia Aging Study (HAAS), Department of Research, Kuakini Medical Center, Honolulu, Hawaii; Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii; Department of Human Welfare, Okinawa International University, Ginowan, Okinawa, Japan;
authors.forename: Donald C
authors.initials: DC
authors.lastname: Willcox
authors.affiliation: Institute for Biogenesis Research, University of Hawaii, Honolulu, Hawaii.
authors.forename: Richard
authors.initials: R
authors.lastname: Allsopp
authors.affiliation: Honolulu Heart Program (HHP)/Honolulu-Asia Aging Study (HAAS), Department of Research, Kuakini Medical Center, Honolulu, Hawaii; Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii;
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Willcox
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006254:Hawaii / Q000453:epidemiology; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D007564:Japan / Q000208:ethnology; D008297:Male; D008875:Middle Aged; D050177:Overweight / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D000076223:Regulatory-Associated Protein of mTOR; D012307:Risk Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C463659:RPTOR protein, human; D000076223:Regulatory-Associated Protein of mTOR
keywords: blood pressure; body weight; essential hypertension; genetic association analysis; hypertension; isolated systolic hypertension; mechanistic target of rapamycin (mTOR); raptor gene (RPTOR); recursive partitioning analysis.