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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  ;  Byung-Wan Lee  ;  Eun Seok Kang  ;  Bong-Soo Cha  ;  Hyun Chul Lee 
 MEDICINE, Vol.94(43) : e1825, 2015 
Journal Title
Issue Date
Aged ; Albuminuria/genetics* ; Case-Control Studies ; Diabetes Mellitus, Type 2/complications* ; Female ; Genotype ; Heme Oxygenase-1/genetics* ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic
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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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Preventive Medicine and Public Health (예방의학교실) > 1. Journal Papers
Yonsei Authors
Kang, Eun Seok(강은석) ORCID logo https://orcid.org/0000-0002-0364-4675
Kim, Beom Seok(김범석) ORCID logo https://orcid.org/0000-0002-5732-2583
Nam, Chung Mo(남정모) ORCID logo https://orcid.org/0000-0003-0985-0928
Lee, Byung Wan(이병완) ORCID logo https://orcid.org/0000-0002-9899-4992
Lee, Yong Ho(이용호) ORCID logo https://orcid.org/0000-0002-6219-4942
Lee, Hyun Chul(이현철)
Jung, Kyu Sik(정규식)
Cha, Bong Soo(차봉수) ORCID logo https://orcid.org/0000-0003-0542-2854
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