Lack of linkage and association of adrenomedulinand its receptor genes in French Caucasian rheumatoid arthritis trio families

Clinical and Experimental Rheumatology

F. Lioté¹  S. Garnier¹  H.-K. Ea¹  T. Bardin¹  B. Uzan¹  S. Lasbleiz¹  C. Asensio¹  F. Cornélis¹  S. Barbet¹  E. Glikmans¹  L. Michou¹  M.-D. Ah Kioon¹ 

关键词: Rheumatoid arthritis;    adrenomedullin;    calcitonin receptor-like receptor;    linkage;    polymorphism.;   

DOI  :  

学科分类：医学（综合）

来源: Pacini Editore SpA

【 摘 要 】

OBJECTIVES:Rheumatoid arthritis (RA) is characterized by hyperplasia of fibro-blast-like synoviocytes (FLSs), in part due to apoptosis resistance. Adrenomedullin, an anti-apoptotic peptide, is secreted more by RA than osteoarthritis FLSs. Adrenomedullin binds to a heterodimeric functional receptor, of calcitonin receptor-like receptor (CRLR) coupled with a receptor activity-modifying protein-2 (RAMP-2), which is also overexpressed by rheumatoid synoviocytes. Since adrenomedullin decreases RA FLS apoptosis, possibly contributing to the development of pannus, study of adrenomedullin and its receptor genes might reveal a linkage and association in French Caucasian RA trio families.METHODS:Within each of 100 families, one RA-affected patient and both parents underwent genotyping for polymorphisms of adrenomedullin, CRLR and RAMP-2, by PCR-restricted fragment-length polymorphism (RFLP) or Taqman 5` allelic discrimination assay. Statistical analysis relied on the transmission disequilibrium test, the affected family-based controls and the genotype relative risk. Haplotypes of CRLR were inferred, and linkage and association studies were performed.RESULTS:No significant transmission disequilibrium or association between the three genes and RA was observed. CRLR haplotypes revealed two major haplotypes, but no significant linkage with RA.CONCLUSIONS:Our findings provided no significant linkage or association of adrenomedullin and CRLR-RAMP-2 genes with RA in the studied trio families. The two CRLR polymorphisms rs3771076 and rs3771084 should be investigated in larger samples.

【 授权许可】

Unknown