Histo-blood group gene polymorphisms as potential genetic modifiers of infection and cystic fibrosis lung disease severity.
BACKGROUND
The pulmonary phenotype in cystic fibrosis (CF) is variable; thus, environmental and genetic factors likely contribute to clinical heterogeneity. We hypothesized that genetically determined ABO histo-blood group antigen (ABH) differences in glycosylation may lead to differences in microbial binding by airway mucus, and thus predispose to early lung infection and more severe lung disease in a subset of patients with CF.


RESULTS
Clinical information and DNA was collected on >800 patients with the DeltaF508/DeltaF508 genotype. Patients in the most severe and mildest quartiles for lung phenotype were enrolled. Blood samples underwent lymphocyte transformation and DNA extraction using standard methods. PCR and sequencing were performed using standard techniques to identify the 9 SNPs required to determine ABO blood type, and to identify the four SNPs that account for 90-95% of Lewis status in Caucasians. Allele identification of the one nonsynonymous SNP in FUT2 that accounts for >95% of the incidence of nonsecretor phenotype in Caucasians was completed using an ABI Taqman assay. The overall prevalence of ABO types, and of FUT2 (secretor) and FUT 3 (Lewis) alleles was consistent with that found in the Caucasian population. There was no difference in distribution of ABH type in the severe versus mild patients, or the age of onset of Pseudomonas aeruginosa infection in the severe or mild groups. Multivariate analyses of other clinical phenotypes, including gender, asthma, and meconium ileus demonstrated no differences between groups based on ABH type.


CONCLUSIONS
Polymorphisms in the genes encoding ABO blood type, secretor or Lewis genotypes were not shown to associate with severity of CF lung disease, or age of onset of P. aeruginosa infection, nor was there any association with other clinical phenotypes in a group of 808 patients homozygous for the DeltaF508 mutation.
Taylor-Cousar
Jennifer L
JL
Pulmonary Division, Internal Medicine and Pediatrics, Albuquerque, New Mexico, University of New Mexico Health Sciences Center, United States of America. JTCousar@salud.unm.edu
Zariwala
Maimoona A
MA
Burch
Lauranell H
LH
Pace
Rhonda G
RG
Drumm
Mitchell L
ML
Calloway
Hollin
H
Fan
Haiying
H
Weston
Brent W
BW
Wright
Fred A
FA
Knowles
Michael R
MR
D000017:ABO Blood-Group System / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D001789:Blood Group Antigens / Q000235:genetics; D003550:Cystic Fibrosis / Q000235:genetics* / Q000382:microbiology* / Q000473:pathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008168:Lung / Q000378:metabolism; D008297:Male; D009093:Mucus / Q000382:microbiology; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011552:Pseudomonas Infections / Q000235:genetics / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000378:metabolism
D000017:ABO Blood-Group System; D001789:Blood Group Antigens