title: The 8.1 ancestral MHC haplotype is associated with delayed onset of colonization in cystic fibrosis.
abstract: Major cause of death in patients with cystic fibrosis (CF) is colonization with Staphylococcus aureus and Pseudomonas aeruginosa. The wide phenotypic variation in CF patients suggests that genes other than the cystic fibrosis transmembrane conductance regulator (CFTR) gene modify the disease. The 8.1 ancestral haplotype (8.1AH) in main histocompatibility complex is associated with alterations of the immune response. To study the influence of carriage of 8.1AH on frequency and onset of colonization in CF patients, DNA samples of 72 CF patients (39 homozygous and 33 heterozygous for DeltaF508) were genotyped for member alleles of the 8.1AH: HLA-DQB1*0201, HLA-DRB1*0301, receptor for advanced glycation end products (AGER) -429C, HSP70-2 -1267G (HSP70-2G) and tumor necrosis factor-alpha (TNF-alpha) -308A (TNF2). Colonization was verified by regular clinical and bacteriological screening. Frequency of colonization was significantly (P = 0.012) lower in the 8.1AH carriers; age, gender and DeltaF508 genotype-adjusted odds ratio to be colonized of the carriers versus non-carriers was 0.112 (0.024-0.520). According to survival analysis, patients with 8.1AH had significantly (P < 0.0001) longer colonization-free period compared with non-carriers. Our novel observations demonstrate that the 8.1AH is associated with delayed onset of colonization in CF, presumably by influencing defense mechanisms against infections.
authors.affiliation: Third Department of Medicine, Semmelweis University, 1125 Budapest, Kútvölgyi út 4, Hungary. lakij@kut.sote.hu
authors.forename: Judit
authors.initials: J
authors.lastname: Laki
authors.forename: István
authors.initials: I
authors.lastname: Laki
authors.forename: Krisztina
authors.initials: K
authors.lastname: Németh
authors.forename: Rita
authors.initials: R
authors.lastname: Ujhelyi
authors.forename: Olga
authors.initials: O
authors.lastname: Bede
authors.forename: Emoke
authors.initials: E
authors.lastname: Endreffy
authors.forename: Katalin
authors.initials: K
authors.lastname: Bolbás
authors.forename: Kálmán
authors.initials: K
authors.lastname: Gyurkovits
authors.forename: Eszter
authors.initials: E
authors.lastname: Csiszér
authors.forename: Eniko
authors.initials: E
authors.lastname: Sólyom
authors.forename: Gergely
authors.initials: G
authors.lastname: Dobra
authors.forename: Adrienn
authors.initials: A
authors.lastname: Halász
authors.forename: Eva
authors.initials: E
authors.lastname: Pozsonyi
authors.forename: Katalin
authors.initials: K
authors.lastname: Rajczy
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Prohászka
authors.forename: György
authors.initials: G
authors.lastname: Fekete
authors.forename: George
authors.initials: G
authors.lastname: Füst
mesh_terms: D000293:Adolescent; D000328:Adult; D001424:Bacterial Infections / Q000150:complications / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000150:complications / Q000235:genetics* / Q000382:microbiology*; D004198:Disease Susceptibility; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D006814:Hungary / Q000453:epidemiology; D007223:Infant; D011110:Polymorphism, Genetic; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000276:immunology; D013211:Staphylococcus aureus / Q000235:genetics / Q000276:immunology
chemical_list: D006680:HLA Antigens