Association between heme oxygenase-1 promoter polymorphisms and the development of albuminuria in type 2 diabetes

A case-control study

Eun Young Lee, Yong Ho Lee, Soo Hyun Kim, Kyu Sik Chung, Obin Kwon, Beom Seok Kim, Chung Mo Nam, Chun Sik Park, byungwan lee, Eun Seok Kang, Bong Soo Cha, Hyun Chul Lee

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Heme oxygenase (HO)-1 is a key enzyme in cytoprotective mechanisms against oxidative stress in the cardiovascular-renal system. The T(-413)A single nucleotide polymorphism (SNP) and (GT)n microsatellite polymorphism in the HO-1 gene promoter modulate the HO-1 gene transcriptional activity and these polymorphisms are associated with various human diseases. We investigated the association between HO-1 promoter polymorphisms and nephropathy in type 2 diabetes. We sequenced the T(-413)A SNP and (GT)n repeat segments of the HO-1 gene promoter in 536 patients with type 2 diabetes. (GT)n alleles were divided into 2 groups: short (S, ≥25 GT repeats) and long (L, <25 GT repeats) alleles. The presence of albuminuria was used as a marker of diabetic nephropathy. Patients with the TT genotype in the T(-413)A SNP were significantly more susceptible to albuminuria development than those carrying the A allele, with an odds ratio of 1.577 (95% confidence interval, 1.088≥2.285; P=0.016). Subgroup analysis showed that patients carrying the TT genotype with long duration of diabetes (≥20 years), poor glycemic control, male gender and without hypertension had higher odds ratios for the development of albuminuria. In vitro, promoter activity of the T(-413)A SNP was higher with A allele than T allele. Regarding to the (GT)n repeats, the LL genotype showed a higher odds ratio for the development of albuminuria only in patients with hypertension when compared to the S allele. In conclusion, the T(-413)A SNP in the HO-1 promoter is significantly associated with albuminuria development in type 2 diabetes patients, especially with longer duration and poor glycemic control.

Original languageEnglish
Article numbere1825
JournalMedicine (United States)
Volume94
Issue number43
DOIs
Publication statusPublished - 2015 Jan 1

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Heme Oxygenase-1
Albuminuria
Type 2 Diabetes Mellitus
Case-Control Studies
Alleles
Single Nucleotide Polymorphism
Odds Ratio
Genotype
Genes
Hypertension
Diabetic Nephropathies
Cardiovascular System
Microsatellite Repeats
Oxidative Stress
Confidence Intervals
Kidney
Enzymes

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Lee, Eun Young ; Lee, Yong Ho ; Kim, Soo Hyun ; Chung, Kyu Sik ; Kwon, Obin ; Kim, Beom Seok ; Nam, Chung Mo ; Park, Chun Sik ; lee, byungwan ; Kang, Eun Seok ; Cha, Bong Soo ; Lee, Hyun Chul. / Association between heme oxygenase-1 promoter polymorphisms and the development of albuminuria in type 2 diabetes : A case-control study. In: Medicine (United States). 2015 ; Vol. 94, No. 43.
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abstract = "Heme oxygenase (HO)-1 is a key enzyme in cytoprotective mechanisms against oxidative stress in the cardiovascular-renal system. The T(-413)A single nucleotide polymorphism (SNP) and (GT)n microsatellite polymorphism in the HO-1 gene promoter modulate the HO-1 gene transcriptional activity and these polymorphisms are associated with various human diseases. We investigated the association between HO-1 promoter polymorphisms and nephropathy in type 2 diabetes. We sequenced the T(-413)A SNP and (GT)n repeat segments of the HO-1 gene promoter in 536 patients with type 2 diabetes. (GT)n alleles were divided into 2 groups: short (S, ≥25 GT repeats) and long (L, <25 GT repeats) alleles. The presence of albuminuria was used as a marker of diabetic nephropathy. Patients with the TT genotype in the T(-413)A SNP were significantly more susceptible to albuminuria development than those carrying the A allele, with an odds ratio of 1.577 (95{\%} confidence interval, 1.088≥2.285; P=0.016). Subgroup analysis showed that patients carrying the TT genotype with long duration of diabetes (≥20 years), poor glycemic control, male gender and without hypertension had higher odds ratios for the development of albuminuria. In vitro, promoter activity of the T(-413)A SNP was higher with A allele than T allele. Regarding to the (GT)n repeats, the LL genotype showed a higher odds ratio for the development of albuminuria only in patients with hypertension when compared to the S allele. In conclusion, the T(-413)A SNP in the HO-1 promoter is significantly associated with albuminuria development in type 2 diabetes patients, especially with longer duration and poor glycemic control.",
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Association between heme oxygenase-1 promoter polymorphisms and the development of albuminuria in type 2 diabetes : A case-control study. / Lee, Eun Young; Lee, Yong Ho; Kim, Soo Hyun; Chung, Kyu Sik; Kwon, Obin; Kim, Beom Seok; Nam, Chung Mo; Park, Chun Sik; lee, byungwan; Kang, Eun Seok; Cha, Bong Soo; Lee, Hyun Chul.

In: Medicine (United States), Vol. 94, No. 43, e1825, 01.01.2015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association between heme oxygenase-1 promoter polymorphisms and the development of albuminuria in type 2 diabetes

T2 - A case-control study

AU - Lee, Eun Young

AU - Lee, Yong Ho

AU - Kim, Soo Hyun

AU - Chung, Kyu Sik

AU - Kwon, Obin

AU - Kim, Beom Seok

AU - Nam, Chung Mo

AU - Park, Chun Sik

AU - lee, byungwan

AU - Kang, Eun Seok

AU - Cha, Bong Soo

AU - Lee, Hyun Chul

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Heme oxygenase (HO)-1 is a key enzyme in cytoprotective mechanisms against oxidative stress in the cardiovascular-renal system. The T(-413)A single nucleotide polymorphism (SNP) and (GT)n microsatellite polymorphism in the HO-1 gene promoter modulate the HO-1 gene transcriptional activity and these polymorphisms are associated with various human diseases. We investigated the association between HO-1 promoter polymorphisms and nephropathy in type 2 diabetes. We sequenced the T(-413)A SNP and (GT)n repeat segments of the HO-1 gene promoter in 536 patients with type 2 diabetes. (GT)n alleles were divided into 2 groups: short (S, ≥25 GT repeats) and long (L, <25 GT repeats) alleles. The presence of albuminuria was used as a marker of diabetic nephropathy. Patients with the TT genotype in the T(-413)A SNP were significantly more susceptible to albuminuria development than those carrying the A allele, with an odds ratio of 1.577 (95% confidence interval, 1.088≥2.285; P=0.016). Subgroup analysis showed that patients carrying the TT genotype with long duration of diabetes (≥20 years), poor glycemic control, male gender and without hypertension had higher odds ratios for the development of albuminuria. In vitro, promoter activity of the T(-413)A SNP was higher with A allele than T allele. Regarding to the (GT)n repeats, the LL genotype showed a higher odds ratio for the development of albuminuria only in patients with hypertension when compared to the S allele. In conclusion, the T(-413)A SNP in the HO-1 promoter is significantly associated with albuminuria development in type 2 diabetes patients, especially with longer duration and poor glycemic control.

AB - Heme oxygenase (HO)-1 is a key enzyme in cytoprotective mechanisms against oxidative stress in the cardiovascular-renal system. The T(-413)A single nucleotide polymorphism (SNP) and (GT)n microsatellite polymorphism in the HO-1 gene promoter modulate the HO-1 gene transcriptional activity and these polymorphisms are associated with various human diseases. We investigated the association between HO-1 promoter polymorphisms and nephropathy in type 2 diabetes. We sequenced the T(-413)A SNP and (GT)n repeat segments of the HO-1 gene promoter in 536 patients with type 2 diabetes. (GT)n alleles were divided into 2 groups: short (S, ≥25 GT repeats) and long (L, <25 GT repeats) alleles. The presence of albuminuria was used as a marker of diabetic nephropathy. Patients with the TT genotype in the T(-413)A SNP were significantly more susceptible to albuminuria development than those carrying the A allele, with an odds ratio of 1.577 (95% confidence interval, 1.088≥2.285; P=0.016). Subgroup analysis showed that patients carrying the TT genotype with long duration of diabetes (≥20 years), poor glycemic control, male gender and without hypertension had higher odds ratios for the development of albuminuria. In vitro, promoter activity of the T(-413)A SNP was higher with A allele than T allele. Regarding to the (GT)n repeats, the LL genotype showed a higher odds ratio for the development of albuminuria only in patients with hypertension when compared to the S allele. In conclusion, the T(-413)A SNP in the HO-1 promoter is significantly associated with albuminuria development in type 2 diabetes patients, especially with longer duration and poor glycemic control.

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