Risk of Wnt/β-catenin signalling pathway gene polymorphisms in primary Sjögren's syndrome

Javier Fernández-Torres, Nonanzit Pérez-Hernández, Gabriela Hernández-Molina, Gabriela A Martínez-Nava, Daniela Garrido-Rodríguez, Alberto López-Reyes, José M Rodríguez-Pérez
Rheumatology 2019 July 13

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.


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