RGD Reference Report - [Polymorphisms in the glutathione peroxidase-1 gene associated with increased risk of Keshan disease]. - Rat Genome Database

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[Polymorphisms in the glutathione peroxidase-1 gene associated with increased risk of Keshan disease].

Authors: Lei, C  Niu, XL  Wei, J  Zhu, JH  Zhu, Y 
Citation: Lei C, etal., Zhonghua Yu Fang Yi Xue Za Zhi. 2010 Jul;44(7):617-21.
RGD ID: 11352821
Pubmed: (View Article at PubMed) PMID:21055077

OBJECTIVE: To assess the association of blood selenium and polymorphism of glutathione peroxidase-1 (GPx-1) genes in patients with Keshan Disease (KD) and provide genetic evidence for KD susceptibility. METHODS: The levels of whole blood selenium and the activity of GPx-1 were measured with spectrophotometric and enzymatic method among 71 KD patients and 290 controls (including 78 internal controls and 212 external controls). The genotype of GPx-1 at 198 site was analyzed by sequencing and PCR-RFLP. The functions of two GPx-1 variants were studied by rat neonatal cardiomyocytes transfection and expression plasmid. RESULTS: Blood level of selenium in KD patients was (0.8 +/- 0.2) micromol/L, the internal controls' was (0.9 +/- 0.2) micromol/L, and the external controls' was (1.2 +/- 0.2) micromol/L (F = 4.888, P < 0.001).GPx-1 activity of KD patients was (73.0 +/- 12.6) x 10(-10)U/RBC, internal controls' was (80.9 +/- 9.2) x 10(-10)U/RBC, and external controls' was (115.8 +/- 21.1) x 10(-10)U/RBC (F = 5.324, P < 0.001). Those of KD patients were significantly lower than controls. The polymorphism (Pro198Leu) of GPx-1 were identified; the frequency of Pro198Leu of KD patients was 21.1%, the frequency of controls was 10.7% (chi(2) = 5.588, P = 0.018). The level of blood selenium in variant subgroup (Pro198Leu or Leu198Leu) was (0.9 +/- 0.2) micromol/L, and its in non-variant subgroup was (1.1 +/- 0.3) micromol/L (t = 3.183, P < 0.01); The GPx-1 activity in variant subgroup was (86.1 +/- 23.0) x 10(-10)U/RBC, and its in non-variant subgroup was (101.8 +/- 25.9) x 10(-10)U/RBC (t = 5.784, P < 0.01). Further analysis revealed a synergistic-multiplicative interaction between presence of GPx-1 codon198 alleles and low blood selenium level. Over-expression of GPx-1 (198Leu) in rat cardiomyocytes caused 30% lower enzyme activity and less response to increasing concentrations of selenium than with over-expression of GPx-1 (198Pro). CONCLUSION: Low blood selenium in carriers with the 198Leu-susceptible genotype of GPx-1 is associated with low GPx-1 activity, synergistic-multiplicative interaction was found between these two factors. And these two factors may increase the risk of KD.


Disease Annotations    
Keshan disease  (IAGP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Gpx1  (glutathione peroxidase 1)

Genes (Mus musculus)
Gpx1  (glutathione peroxidase 1)

Genes (Homo sapiens)
GPX1  (glutathione peroxidase 1)

Additional Information