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Titolo:
Microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with susceptibility to emphysema
Autore:
Yamada, N; Yamaya, M; Okinaga, S; Nakayama, K; Sekizawa, K; Shibahara, S; Sasaki, H;
Indirizzi:
Tohoku Univ, Sch Med, Dept Geriatr & Resp Med, Aoba Ku, Sendai, Miyagi 9808574, Japan Tohoku Univ Sendai Miyagi Japan 9808574 Ku, Sendai, Miyagi 9808574, Japan Tohoku Univ, Sch Med, Dept Mol Biol & Appl Physiol, Aoba Ku, Sendai, Miyagi 9808574, Japan Tohoku Univ Sendai Miyagi Japan 9808574 Ku, Sendai, Miyagi 9808574, Japan Univ Tsukuba, Inst Clin Med, Dept Pulm Med, Tsukuba, Ibaraki 305, Japan Univ Tsukuba Tsukuba Ibaraki Japan 305 m Med, Tsukuba, Ibaraki 305, Japan
Titolo Testata:
AMERICAN JOURNAL OF HUMAN GENETICS
fascicolo: 1, volume: 66, anno: 2000,
pagine: 187 - 195
SICI:
0002-9297(200001)66:1<187:MPITHO>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
CIGARETTE-SMOKING; IDENTIFICATION; TRANSCRIPTION; EXPRESSION; INDUCTION; ALPHA-1-ANTITRYPSIN; UPSTREAM; DISEASE; ELEMENT; STRESS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
33
Recensione:
Indirizzi per estratti:
Indirizzo: Sasaki, H Tohoku Univ, Sch Med, Dept Geriatr & Resp Med, Aoba Ku, Seiryo Machi 1-1, Sendai, Miyagi 9808574, Japan Tohoku Univ Seiryo Machi 1-1 SendaiMiyagi Japan 9808574 , Japan
Citazione:
N. Yamada et al., "Microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with susceptibility to emphysema", AM J HU GEN, 66(1), 2000, pp. 187-195

Abstract

Cigarette smoke, containing reactive oxygen species, is the most importantrisk factor for chronic pulmonary emphysema (CPE). Heme oxygenase-1 (HO-1)plays a protective role as an antioxidant in the lung. A (GT)(n) dinucleotide repeat in the 5'-flanking region of human HO-1 gene-shows length polymorphism and could modulate the level of gene transcription. To investigate the correlation between the length of the (GT), repeat and susceptibility tothe development of CPE, we screened the frequencies of alleles with varying numbers of (GT)(n) repeats in the HO-1 gene in 101 smokers with CPE and in 100 smokers without CPE. Polymorphisms of the (GT)(n) repeat were groupedinto three classes: class S alleles (<25 repeats), class M alleles (25-29 repeats), and class L alleles (greater than or equal to 30 repeats). The proportion of allele frequencies in class L, as well as the proportion of genotypic frequencies in the group with class L alleles (L/L, L/M, and L/S), was significantly higher in the smokers with CPE than in smokers without CPE. Moreover, we analyzed the promoter activities of the HO-1 gene carrying different (GT())n repeats (n = 16, 20, 29, and 38), by transient-transfection assay in cultured cell lines. H2O2 exposure up-regulated the transcriptional activity of the HO-1 promoter/luciferase fusion genes with (GT)(16) or (GT)(20) but did not do so with (GT)(29) or (GT)(38). These findings suggest that the large size of a (GT), repeat in the HO-1 gene promoter may reduce HO-1 inducibility by reactive oxygen species in cigarette smoke, thereby resulting in the development of CPE.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/07/20 alle ore 22:02:09