Interaction of glutathione peroxidase-1 and selenium in endemic dilated cardiomyopathy.

Abstract

BACKGROUND:

Keshan disease (KD) is a fatal dilated cardiomyopathy with unknown etiology. We studied the gene-environment interaction in the pathogenesis of KD by assessing the association of low blood selenium and polymorphisms in glutathione peroxidase-1 (GPx-1) gene.

METHODS:

The concentration of blood selenium and the activity and polymorphisms of GPx-1 in 71KD patients and 290 controls were measured. The functions of rat neonatal cardiomyocytes resulting from overexpression of 2 variants of GPx-1 were studied.

RESULTS:

Blood concentration of selenium and GPx-1 activity were lower in patients than in controls. Genetic analysis revealed a single nucleotide polymorphism (Pro198Leu) in GPx-1 gene associated with selenium deficiency as well as impaired GPx-1 activity. Gene-environment interaction analysis revealed a synergistic-multiplicative interaction between polymorphism of GPx-1 and selenium deficiency. Overexpression of the GPx-1 leucine-containing allele in cultured cardiomyocytes caused a 30% reduction in selenium-induced GPx-1 activity and increased serum starvation induced apoptosis as compared with that of the wild-type variant 198Pro.

CONCLUSION:

Selenium deficiency in carriers with the GPx-1 leucine-containing allele is associated with low GPx-1 enzyme activity, which may, in turn, increase the incidence of KD. Results from this unique disease may have broad implications for a gene-environment reaction in the etiology of other diseases.

• Authors: Cong Lei, Xiaolin Niu, Jin Wei, Jianhong Zhu, Yi Zhu
• Journal: Clinica chimica acta; international journal of clinical chemistry (Clin Chim Acta) Vol. 399 Issue 1-2 Pg. 102-8 (Jan 2009) ISSN: 1873-3492 [Electronic] Netherlands
• PMID: 18940188 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glutathione Peroxidase
• Leucine
• Selenium
• Glutathione Peroxidase GPX1

Topics

• Aged
• Alleles
• Animals
• Animals, Newborn
• Apoptosis (physiology)
• Base Sequence
• Cardiomyopathy, Dilated (blood, genetics, pathology)
• Case-Control Studies
• Cells, Cultured
• Clinical Enzyme Tests
• Genotype
• Glutathione Peroxidase (blood, genetics, metabolism)
• Humans
• Leucine (genetics)
• Myocytes, Cardiac (metabolism, pathology)
• Polymorphism, Genetic
• Rats
• Selenium (blood, deficiency)
• Glutathione Peroxidase GPX1