title: Relationship between HLA-DR, HLA-DQ alleles and MEFV gene mutations in familial Mediterranean fever (FMF) patients.
abstract: OBJECTIVE
  Three missense mutations clustered on the carboxyl-terminal portion of the MEFV gene (M680I, M694V, and V726A) have been observed in over 80% of affected alleles in several ethnic groups of familial Mediterranean fever patients. Several immunologic abnormalities were found both in cellular and humoral components in Mediterranean fever patients. Those observations have pointed the way for analysis of the HLA region in Mediterranean fever. We intended to compare HLA DR/DQ alleles with those major mutations in the MEFV gene in Mediterranean fever patients.
  
  
  METHODS
  The distribution of MEFV gene mutations and HLA-DR, HLA-DQ alleles were analyzed in 40 index Turkish Mediterranean fever patients, 28 family members and 42 healthy controls. M680I, M694V, and V726A mutations were studied by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) analysis. HLA-DR and DQ allele subgroups were studied using SSP-PCR technique.
  
  
  RESULTS
  A total of 37 (92.5%) patients in 40 Mediterranean fever index patients were found to carry one of the three missense mutations. The HLA-DR4 allele frequency was significantly higher in the Mediterranean fever patient group. When comparisons were made between Mediterranean fever mutations and HLA allele frequencies, M694V mutation with HLA DR3, DR11/5 and DR 13/6 and M680I mutation with DR7 allele subgroups were statistically significant. DQ6/1, DQ7/3, and DQ8/3 allele with M694V, DQ2 allele with M680I, and DQ6/1 with V726A mutations were also statistically significant.
  
  
  CONCLUSIONS
  Our results indicate a relationship between some HLA-DR/DQ alleles and MEFV mutations in Mediterranean fever patients. We suggest HLA-DR/DQ alleles and their role in the pathogenesis of Mediterranean fever need further analysis and comparative studies.
authors.affiliation: Department of Clinical Immunology, School of Medicine, Ankara University, Ankara, Turkey. gkinikli@hotmail.com
authors.forename: Gülay
authors.initials: G
authors.lastname: Kinikli
authors.forename: Mehmet
authors.initials: M
authors.lastname: Bektaş
authors.forename: Müge
authors.initials: M
authors.lastname: Misirlioğlu
authors.forename: Aşkin
authors.initials: A
authors.lastname: Ateş
authors.forename: Murat
authors.initials: M
authors.lastname: Turgay
authors.forename: Serdar
authors.initials: S
authors.lastname: Tuncer
authors.forename: Sami
authors.initials: S
authors.lastname: Kinikli
authors.forename: Güner
authors.initials: G
authors.lastname: Tokgöz
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D003598:Cytoskeletal Proteins / Q000235:genetics*; D010505:Familial Mediterranean Fever / Q000235:genetics*; D005500:Follow-Up Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D000071198:Pyrin; D014421:Turkey
chemical_list: D003598:Cytoskeletal Proteins; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; C000604192:MEFV protein, human; D000071198:Pyrin