Association Between Heme Oxygenase-1 Promoter Polymorphisms and the Development of Albuminuria in Type 2 Diabetes: A Case–Control Study. Issue 43 (October 2015)

• Record Type: Journal Article
• Authors: Lee, Eun Young; Lee, Yong-ho; Kim, Soo Hyun; Jung, 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
• Editors: Xu., Jinxian
• Is Part Of: Medicine. Volume 94:Issue 43(2015)
• Page Start: e1825
• Publication Date: 2015-10
• Subjects: Medicine -- Periodicals; Medicine -- Periodicals; Médecine -- Périodiques; Geneeskunde; Medicine; Periodicals; Periodicals; 610.5
• DOI: 10.1097/MD.0000000000001825
• Languages: English
• ISSNs: 0025-7974

Abstract

Abstract : 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.