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.
Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan. myamada.epi@mri.tmd.ac.jp
Miki
M
Yamada
Takeo
T
Ishii
Shinobu
S
Ikeda
Makiko
M
Naka-Mieno
Noriko
N
Tanaka
Tomio
T
Arai
Toshio
T
Kumasaka
Akihiko
A
Gemma
Kozui
K
Kida
Masaaki
M
Muramatsu
Motoji
M
Sawabe
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000235:genetics; D011656:Pulmonary Emphysema / Q000150:complications / Q000235:genetics*
D005647:Fucosyltransferases; C020559:Glycoprotein 6-alpha-L-fucosyltransferase