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Fucosyltransferase 8 (FUT8) Polymorphism, Thr267Lys, Is Associated With Pulmonary Emphysema FREE TO VIEW

Miki Yamada, MD; Takeo Ishii, MD; Shinobu Ikeda, MD; Kozui Kida, MD; Masaaki Muramatsu, MD; Motoji Sawabe, MD
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Department of Molocular Epidemiology, Tokyo Medical and Dental University, Tokyo, Japan

Chest. 2011;140(4_MeetingAbstracts):553A. doi:10.1378/chest.1112951
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PURPOSE: The fucosyltransferase 8 gene (FUT8) encodes α1,6-fucosyltransferase, an essential enzyme that transfers fucose to the innermost N-acetylglucosamine unit of N-glycan chains. Recent study showed that fut8-deficient mice develop pathological and physiological phenotypes resembling pulmonary emphysema (PE). The role of FUT8 in human PE is not known.

METHODS: A non-synonymous single nucleotide polymorphism (SNP) at the amino acid position of 267 in FUT8 (rs35949016; C/A, C allele=Thr, A allele=Lys) was genotyped in a total of 1149 consecutive autopsies of elderly Japanese persons. A second study included 182 outpatients with COPD, whose emphysematous changes were assessed quantitatively as the percentage of low attenuation area (%LAA) by high-resolution computed tomography.

RESULTS: In the first study, PE was detected in 163 of 1149 autopsy subjects (14.2%). Comparison of patient with versus without PE indicated that the FUT8 A allele was associated with PE (AA+AC vs CC; OR= 1.74, 95% CI = 1.19-2.56, p = 0.005). In the second study, presence of the FUT8 A allele significantly correlated with %LAA after adjustment (AA+AC vs. CC = 37.5±14.7 vs. 32.7±13.9, p = 0.02).

CONCLUSIONS: The FUT8 gene Thr267Lys polymorphism is associated with human PE, and the A allele, which encodes Lys267, is the risk allele for emphysema. The role of core fucosylation in the molecular pathogenesis of human PE warrants further study.

CLINICAL IMPLICATIONS: Our results imply that regulation of core fucosylation may be an important step in the molecular pathogenesis of human pulmonary emphysema, which provides a potential target for innovative therapies.

DISCLOSURE: The following authors have nothing to disclose: Miki Yamada, Takeo Ishii, Shinobu Ikeda, Kozui Kida, Masaaki Muramatsu, Motoji Sawabe

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