Identification of a novel 5-base pair deletion in calcineurin B (PPP3R1) promoter region and its association with left ventricular hypertrophy

Weihong Tang, Donna K. Arnett, Richard B. Devereux, Demetrios Panagiotou, Michael A. Province, Michael B. Miller, Giovanni De Simone, Charles Gu, Robert E. Ferrell

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


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/m2.7 in men and >47 g/m2.7 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.

Original languageEnglish
Pages (from-to)845-851
Number of pages7
JournalAmerican Heart Journal
Issue number4
StatePublished - Oct 2005

Bibliographical note

Funding Information:
The HyperGEN network is funded by NHLBI R01 HL55673 and cooperative agreements (U10) with NHLBI: HL54471, HL54515 (UT), HL54472, HL54496 (MN), HL54473 (MO), HL54495 (AL), HL54509 (NC). This study is also partly supported by NIH grant U10HL54526. Doctor Tang is supported by NHLBI training grant 1T32-HL07972.

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


Dive into the research topics of 'Identification of a novel 5-base pair deletion in calcineurin B (PPP3R1) promoter region and its association with left ventricular hypertrophy'. Together they form a unique fingerprint.

Cite this