Novel association of HLA-haplotypes with primary sclerosing cholangitis (PSC) in a southern European population.
OBJECTIVE
In patients with with primary sclerosing cholangitis we investigated the major histocompatibility complex (MHC) genes and mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene.


METHODS
In 64 PSC patients and 183 normal controls of the same population (Northern Italy), allelic polymorphisms at the DNA level were investigated in MHC region genes: HLA-DRB1, HLA-DQB1 and HLA-B, tumour necrosis factor A (TNFA), and in CFTR gene, with polymerase chain reaction-based methodologies.


RESULTS
Frequencies of DRB1*01, DQA1*0101, DQB1*0102 (14 vs. 8%, p<0.05), DRB1*16, DQA1*0102, DQB1*0502 (8 vs. 3%, p<0.025) and DRB1*04, DQA1*03, DQB1*0301 (10 vs. 4%, p<0.005) haplotypes were more elevated in PSC patients. The frequency of patients positive for HLA DRB1*01, *1601 or *04 related haplotypes was significantly increased (32 vs. 14%, p<0.00025). DRB1*07, DQA1*0201, DQB1*02 haplotype frequency was significantly decreased (4 vs. 15%, p<0.001). After removing HLA-DRB1*01, *1601, *04 related haplotype sharing patients, HLA-DRB1*03, DQA1*0501, DQB1*02 haplotype frequency was significantly increased (32 vs. 14%, p<0.01). TNFA2 allele frequency was significantly increased in PSC patients (23 vs. 14%, p<0.025), as well as the TNFA2 homozygous genotype (9 vs. 0.5%, p=0.0013). No mutations were found on the CFTR gene and the allelic frequency of the 5T polymorphism in intron 8 was not increased.


CONCLUSIONS
These data suggest that the role of genes in the HLA region is relevant, but not necessarily disease-specific and it might be different in populations with divergent ancestries.
Department of Internal Medicine, Nephrology and Health Sciences, University of Parma, Parma, Italy.
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TM
Neri
G M
GM
Cavestro
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P
Seghini
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PF
Zanelli
A
A
Zanetti
M
M
Savi
M
M
Podda
M
M
Zuin
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M
Colombo
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A
Floreani
F
F
Rosina
G
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Bianchi Porro
M
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Strazzabosco
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Okolicsanyi
D000328:Adult; D016022:Case-Control Studies; D015209:Cholangitis, Sclerosing / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005828:Genetics, Population; D005838:Genotype; D015235:HLA-B Antigens / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
C505032:CFTR protein, human; D015235:HLA-B Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D014409:Tumor Necrosis Factor-alpha; D019005:Cystic Fibrosis Transmembrane Conductance Regulator