Genetic Variation in the Raptor Gene Is Associated With Overweight But Not Hypertension in American Men of Japanese Ancestry

• Published in: American journal of hypertension Vol. 28; no. 4; pp. 508 - 517
• Main Authors: Morris, Brian J., Carnes, Bruce A., Chen, Randi, Donlon, Timothy A., He, Qimei, Grove, John S., Masaki, Kamal H., Elliott, Ayako, Willcox, Donald C., Allsopp, Richard, Willcox, Bradley J.
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.04.2015
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Aged; Aged, 80 and over; Asian Continental Ancestry Group - genetics; Case-Control Studies; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Genetics; Hawaii - epidemiology; Humans; Hypertension - diagnosis; Hypertension - ethnology; Hypertension - genetics; Japan - ethnology; Male; Middle Aged; Original; Overweight - diagnosis; Overweight - ethnology; Overweight - genetics; Phenotype; Polymorphism, Single Nucleotide; Regulatory-Associated Protein of mTOR; Risk Factors; body weight; blood pressure; mechanistic target of rapamycin (mTOR); raptor gene (RPTOR); genetic association analysis; isolated systolic hypertension; essential hypertension; recursive partitioning analysis; hypertension
• ISSN: 0895-7061; 1941-7225; 1941-7225
• DOI: 10.1093/ajh/hpu188

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.