Association of fucosyltransferase 8 (FUT8) polymorphism Thr267Lys with pulmonary emphysema.

The fucosyltransferase 8 gene (FUT8) encodes an 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. A non-synonymous single-nucleotide polymorphism 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. A following study included 182 outpatients with chronic obstructive pulmonary disease, whose emphysematous changes were assessed quantitatively as the percentage of low attenuation area (%LAA) by high-resolution computed tomography. PE was detected in 163 of 1149 autopsy subjects (14.2%). Comparison of patient with vs without PE indicated that the FUT8 A allele was associated with PE (AA+AC vs CC; odds ratio=1.74, 95% confidence intervals=1.19-2.56, P=0.005). In the clinical 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). The FUT8 gene Thr267Lys polymorphism is associated with human PE, and the Lys allele is the risk. The core fucosylation might be involved in the molecular pathogenesis of human PE.