J Korean Med Sci.  2009 Jan;24(Suppl 1):S30-S37. 10.3346/jkms.2009.24.S1.S30.

The Heme Oxygenase-1 Genotype is a Risk Factor to Renal Impairment of IgA Nephropathy at Diagnosis, Which is a Strong Predictor of Mortality

• Chin HJ
• Cho HJ
• Lee TW
• Na KY
• Yoon HJ
• Chae DW
• Kim S
• Jeon US
• Do JY
• Park JW
• Yoon KW
• Shin YT
• Lee KW
• Na KR
• Cha DR
• Kang YS
• The Progressive REnal disease and Medical Informatics and gEnomics Research (PREMIER) members

• KMID: 1778137
• DOI: http://doi.org/10.3346/jkms.2009.24.S1.S30

Abstract

The induction of heme oxygenase-1 (HO-1) ameliorates oxidative stress and inflammatory process, which play important roles in IgA nephropathy. We hypothesized length polymorphism in the promoter region of the HO-1 gene, which is related to the level of gene transcription, is associated with disease severity of IgA nephropathy. The subjects comprised 916 patients with IgA nephropathy and gene data. Renal impairment was defined as an estimated glomerular filtration rate less than 60 mL/min/1.73 m(2) at diagnosis. The short (S: <23), medium (M: 23-28), and long (L: >28) (GT) repeats in the HO-1 gene was determined. The frequencies of S/S, S/M, M/M, S/L, L/M, and L/L genotypes were 7.2%, 6.9%, 3.1%, 30.8%, 22.7%, and 29.4%, respectively. The baseline characteristics were not different. In the S/S genotypic group, the renal impairment rate was 18.2%, which was lower than 32.2% in the group with M/M, L/M, or L/L genotype. The odds ratio of renal impairment in S/S genotype, compared to that in M/M, L/M, or L/L genotype, was 0.216 (95% confidence interval, 0.060-0.774, p=0.019). The HO-1 gene promoter length polymorphism was related to the renal impairment of IgA nephropathy at diagnosis, which is an important risk factor for mortality in IgA nephropathy patients.

Keyword

Heme Oxygenase; Glomerulonephritis, IGA; Renal Insufficiency

MeSH Terms

Adult
Disease Progression
Female
Gene Frequency
Genotype
Glomerular Filtration Rate
Glomerulonephritis, IGA/*genetics/mortality/*pathology
Heme Oxygenase-1/*genetics
Humans
Male
Middle Aged
Odds Ratio
Polymorphism, Genetic
Promoter Regions, Genetic
Risk Factors

Figure

• 

  Fig. 1 Frequency distribution of number of (GT)n repeats in all IgA patients.

• 

  Fig. 2 Frequency of eGFR less than 60 mL/min/1.73 m2 according to genotypes of the HO-1 promoter region. *, compared between genotype group 1 and group 3; p=0.021.

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