Identification of a novel 5-base pair deletion in calcineurin B (PPP3R1) promoter region and its association with left ventricular hypertrophy.
BACKGROUND
Calcineurin is a calcium/calmodulin-regulated protein phosphatase that functions as a key mediator of hypertrophic response of the heart. Calcineurin B (CnB) is a regulatory subunit of calcineurin and is important for the phosphatase activity.


METHODS
We identified a novel 5-base pair (bp) insertion/deletion (5I/5D) polymorphism within the CnB promoter region and investigated its association with left ventricular hypertrophy (LVH) in 368 severe hypertensive participants (53% African Americans) in the Hypertension Genetic Epidemiology Network study. Traditionally defined LVH was identified by LV mass index >50 g/m(2.7) in men and >47 g/m(2.7) in women. Left ventricular mass predicted from sex, stroke work, and height(2.7) was calculated according to an equation derived from a normal population, and inappropriately high LV mass was defined as observed/predicted LV mass >1.28 based on the equation.


RESULTS
The CnB 5I/5D variation was not significantly associated with the traditionally defined LVH. However, there was a significant association between the CnB 5I/5D polymorphism and presence of inappropriately high LV mass. The ethnicity-adjusted ORs for the 5I/5D and 5D/5D genotypes compared with the 5I/5I genotype was 1.23 (95% CI 0.66-2.28) and 3.05 (95% CI 1.28-7.29) (P = .02 for trend test). This association was independent of age, sex, body mass index, heart rate, prevalent coronary heart disease, and/or diabetes and antihypertensive medications.


CONCLUSIONS
The 5-base pair deletion within the CnB gene may cause excessive LV growth beyond the level appropriate for cardiac workload when exposed to severe hypertension or may be in linkage disequilibrium with the causal mutation.
Tang
Weihong
W
Division of Epidemiology, University of Minnesota, Minneapolis, Minnesota, USA.
Arnett
Donna K
DK
Devereux
Richard B
RB
Panagiotou
Demetrios
D
Province
Michael A
MA
Miller
Michael B
MB
de Simone
Giovanni
G
Gu
Charles
C
Ferrell
Robert E
RE
D001741:Black or African American; D001483:Base Sequence; D019703:Calcineurin / Q000235:genetics*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D017384:Sequence Deletion; D013599:Systole; D044465:White People
D019703:Calcineurin