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: PMID:21055077   (View Abstract at PubMed)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Keshan disease  IAGP 11352821DNA:polymorphism: :p.P198L (human)RGD 
Keshan disease  ISOGPX1 (Homo sapiens)11352821; 11352821DNA:polymorphism: :p.P198L (human)RGD 

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