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European Journal of Heart Failure 2005 7(6):958-965; doi:10.1016/j.ejheart.2004.06.009
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© 2005 European Society of Cardiology

hUNC-93B1, a novel gene mainly expressed in the heart, is related to left ventricular diastolic function, heart failure morbidity and mortality in elderly men

Johan Ärnlöva,*, Johan Sundströma, Lars Lindb, Bertil Andrénb, Maria Anderssona, Richard Renelanda,d, Lars Berglundc, Vladimir Kashubae, Alexei Protopopove, Eugene Zabarovskye and Hans Lithella

a Department of Public Health and Caring Sciences/Geriatrics PO Box 609, S-75125 Uppsala, Sweden
b Department of Medical Sciences, Uppsala University Sweden
c Uppsala Clinical Research Center, Uppsala University Sweden
d Sequenom Inc., San Diego USA
e Microbiology and Tumor Center and Center for Genomics and Bioinformatics, Karolinska Institute Sweden

* Corresponding author. Tel.: +46 18 6117972; fax: +46 18 6117976. E-mail address: Johan.Arnlov{at}pubcare.uu.se


  Abstract

Aims: The hUNC-93B1 gene has the highest expression in the heart. We aimed to explore relationships between the hUNC-93B1 gene and cardiac function, morbidity and mortality in elderly men.

Methods and results: Two sub-samples of the population-based ULSAM-cohort (n=330, mean age 71 years and n=152, mean age 75 years, respectively) were used to explore and validate relationships between genotypes of the hUNC-93B1 gene and cardiac phenotypes (ejection fraction, E/A-ratio, left ventricular mass index and relative wall thickness). In the two samples, subjects homozygous for haplotype H3 had 34% and 35% higher level of E/A-ratio compared to non-carriers (p=0.0002 and 0.017, respectively) independent of cardiovascular disease and medication. Using national cause-of-death and hospital-discharge register data with 29 years of follow-up, no heart failure patients homozygous for haplotype H3 were hospitalised for heart failure before the age of 75 years, compared to 25% for heterozygous and 55% for non-carriers (p<0.03). No homozygous subjects died during follow-up while 17% of the heterozygous and 15% of the non-carriers died (p=0.01).

Conclusion: Haplotype H3 of the hUNC-93B1 gene seems related to E/A-ratio in elderly men. The relationship between the hUNC-93B1 gene and the age at onset of heart failure and mortality support a view of a clinically relevant impact of the gene.

Key Words: Heart failure • Echocardiography • Genes • Left ventricular diastolic function

Received April 6, 2004; Revised May 14, 2004; Accepted June 10, 2004


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