Epistatic effects of ACE I/D and AGT gene variants on left ventricular mass in hypertensive patients: the HyperGEN study.
Identifying predictors of left ventricular hypertrophy has been an active study topic because of its association with cardiovascular morbidity and mortality. We examined the epistatic effect (gene-gene interaction) of two genes (angiotensin-converting enzyme (ACE) insertion/deletion (I/D); angiotensinogen (AGT) -6G-A, M235T, -20A-C) in the renin-angiotensin system on left ventricular mass (LVM) among hypertensive participants in the Hypertension Genetic Epidemiology Network study. Included were 2156 participants aged 20-87 years (60% women, 63% African American). We employed mixed linear regression models to assess main effects of four genetic variants on echocardigraphically determined LVM (indexed for height), and ACE-by-AGT epistatic effects. There was evidence that AGT -6G-A was associated with LVM among white participants: adjusted mean LVM (gm(-2.7)) increased with 'G' allele copy number ('AA':41.2, 'AG':42.3, 'GG':44.0; P=0.03). There was also evidence of an ACE I/D-by-AGT -20A-C epistatic effect among white participants (interaction P=0.03): among ACE 'DD' participants, AGT -20A-C 'C' allele carriers had lower mean LVM than 'AA' homozygotes ('DD/CC':39.2, 'DD/AC':39.9, 'DD/AA':43.9), with no similar significant effect among ACE 'I' allele carriers ('ID/CC':47.2, 'ID/AC':43.4, 'ID/AA':42.6; 'II/CC': NA, 'II/AC':41.3, 'II/AA':43.1). These findings indicate that renin-angiotensin system variants in at least two genes may interact to modulate LVM.
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
A I
AI
Lynch
W
W
Tang
G
G
Shi
R B
RB
Devereux
J H
JH
Eckfeldt
D K
DK
Arnett
D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D000808:Angiotensinogen / Q000235:genetics*; D016009:Chi-Square Distribution; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006720:Homozygote; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D017379:Hypertrophy, Left Ventricular / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D010641:Phenotype; D018570:Risk Assessment; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics; D055815:Young Adult
C534931:AGT protein, human; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A
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