Literature DB >> 25249372

Genetic variation in the raptor gene is associated with overweight but not hypertension in American men of Japanese ancestry.

Brian J Morris1, Bruce A Carnes2, Randi Chen3, Timothy A Donlon3, Qimei He3, John S Grove4, Kamal H Masaki5, Ayako Elliott3, Donald C Willcox6, Richard Allsopp7, Bradley J Willcox5.   

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).
CONCLUSION: 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. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Entities:  

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.

Mesh:

Substances:

Year:  2014        PMID: 25249372      PMCID: PMC4425837          DOI: 10.1093/ajh/hpu188

Source DB:  PubMed          Journal:  Am J Hypertens        ISSN: 0895-7061            Impact factor:   2.689


  35 in total

Review 1.  mTOR signaling in growth control and disease.

Authors:  Mathieu Laplante; David M Sabatini
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Review 3.  Metabolic regulation, mitochondria and the life-prolonging effect of rapamycin: a mini-review.

Authors:  Yong Pan; Yuya Nishida; Margaret Wang; Eric Verdin
Journal:  Gerontology       Date:  2012-08-30       Impact factor: 5.140

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Review 5.  mTOR is a key modulator of ageing and age-related disease.

Authors:  Simon C Johnson; Peter S Rabinovitch; Matt Kaeberlein
Journal:  Nature       Date:  2013-01-17       Impact factor: 49.962

6.  Gene expression analysis of mTOR pathway: association with human longevity.

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Journal:  Aging Cell       Date:  2012-11-23       Impact factor: 9.304

7.  Skeletal muscle-specific ablation of raptor, but not of rictor, causes metabolic changes and results in muscle dystrophy.

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9.  Allele-specific down-regulation of RPTOR expression induced by retinoids contributes to climate adaptations.

Authors:  Chang Sun; Catherine Southard; David B Witonsky; Ralf Kittler; Anna Di Rienzo
Journal:  PLoS Genet       Date:  2010-10-28       Impact factor: 5.917

10.  Rapamycin fed late in life extends lifespan in genetically heterogeneous mice.

Authors:  David E Harrison; Randy Strong; Zelton Dave Sharp; James F Nelson; Clinton M Astle; Kevin Flurkey; Nancy L Nadon; J Erby Wilkinson; Krystyna Frenkel; Christy S Carter; Marco Pahor; Martin A Javors; Elizabeth Fernandez; Richard A Miller
Journal:  Nature       Date:  2009-07-08       Impact factor: 49.962

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3.  Podocyte-specific deletion of tubular sclerosis complex 2 promotes focal segmental glomerulosclerosis and progressive renal failure.

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