The 8.1 ancestral MHC haplotype is associated with delayed onset of colonization in cystic fibrosis.
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.
Laki
Judit
J
Third Department of Medicine, Semmelweis University, 1125 Budapest, Kútvölgyi út 4, Hungary. lakij@kut.sote.hu
Laki
István
I
Németh
Krisztina
K
Ujhelyi
Rita
R
Bede
Olga
O
Endreffy
Emoke
E
Bolbás
Katalin
K
Gyurkovits
Kálmán
K
Csiszér
Eszter
E
Sólyom
Eniko
E
Dobra
Gergely
G
Halász
Adrienn
A
Pozsonyi
Eva
E
Rajczy
Katalin
K
Prohászka
Zoltán
Z
Fekete
György
G
Füst
George
G
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
D006680:HLA Antigens