Affiliation:
1. Synovial Fluid Laboratory, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra
2. Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez
3. Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
4. Center of Research in Infectious Diseases (CIENI), Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico
Abstract
Abstract
Objective
To explore genetic polymorphisms of the Wnt/β-catenin signalling pathway in primary SS (PSS).
Methods
We included 98 patients with PSS and 165 healthy volunteers. Genomic DNA was extracted from peripheral blood samples. Through an open-array platform of low density, we genotyped 25 polymorphisms from 14 genes (WISP1, DKK1, SOST, FRZB, LRP1, LRP4, LRP5, LRP6, GSKB, ADAMTS5, GDF5, FMN2, ADIPOQ and COL11A1) involved in the Wnt/β-catenin signalling pathway. We compared the allelic and genotypic frequencies with Fisher’s exact test and logistic regression analysis adjusted by age, gender and individual admixture, as well as bootstrap-resampling analysis. We assessed the gene–gene interaction by the multifactor dimensionality reduction method.
Results
We found a positive significant association with four polymorphisms: LRP5 rs606989, FRZB rs409238, GSK3B rs2037547 and ADIPOQ rs2241766. All of them conferred risk for PSS, being the highest among subjects carrying three to four risk alleles (P < 0.001). According to a multifactor dimensionality reduction analysis, the best models included the LRP5 (rs606989), FRZB (rs409238) and ADIPOQ (rs2241766) polymorphisms.
Conclusion
LRP5, FRZB and ADIPOQ genes related in the Wnt/β-catenin signalling pathway increased the risk of PSS. Further research is needed to establish their functional role in this clinical entity.
Publisher
Oxford University Press (OUP)
Subject
Pharmacology (medical),Rheumatology
Cited by
12 articles.
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