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 language | English |
|---|---|
| Article number | e1825 |
| Journal | Medicine (United States) |
| Volume | 94 |
| Issue number | 43 |
| DOIs | |
| Publication status | Published - 2015 Jan 1 |
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- Medicine(all)
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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, Byung Wan; 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 journal › Article
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, Byung Wan
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.
UR - http://www.scopus.com/inward/record.url?scp=84946542683&partnerID=8YFLogxK
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U2 - 10.1097/MD.0000000000001825
DO - 10.1097/MD.0000000000001825
M3 - Article
C2 - 26512585
AN - SCOPUS:84946542683
VL - 94
JO - Medicine (United States)
JF - Medicine (United States)
SN - 0025-7974
IS - 43
M1 - e1825
ER -