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Connective Tissue Research Volume 60, 2019 - Issue 3
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Original Articles

Common gene variants interactions related to uric acid transport are associated with knee osteoarthritis susceptibility

Javier Fernández-TorresMusculoskeletal and Rheumatic Diseases Division, Synovial Fluid Laboratory, National Institute of Rehabilitation “Luis Guillermo Ibarra Ibarra”, Mexico City, MexicoORCID Iconhttp://orcid.org/0000-0002-7271-2862
ORCID Icon,
Gabriela Angélica Martínez-NavaMusculoskeletal and Rheumatic Diseases Division, Synovial Fluid Laboratory, National Institute of Rehabilitation “Luis Guillermo Ibarra Ibarra”, Mexico City, MexicoORCID Iconhttp://orcid.org/0000-0001-9857-3840
ORCID Icon,
Francesca OlivieroRheumatology Unit, Department of Medicine - DIMED, University of Padova, Padova, ItalyORCID Iconhttp://orcid.org/0000-0002-4958-5105
ORCID Icon,
Alberto Gabriel López-ReyesMusculoskeletal and Rheumatic Diseases Division, Synovial Fluid Laboratory, National Institute of Rehabilitation “Luis Guillermo Ibarra Ibarra”, Mexico City, MexicoORCID Iconhttp://orcid.org/0000-0002-2575-2589
ORCID Icon,
Karina Martínez-FloresMusculoskeletal and Rheumatic Diseases Division, Synovial Fluid Laboratory, National Institute of Rehabilitation “Luis Guillermo Ibarra Ibarra”, Mexico City, MexicoORCID Iconhttp://orcid.org/0000-0003-0675-0227
ORCID Icon,
Daniela Garrido-RodríguezCIENI, Center for Research in Infectious Diseases, National Institute of Respiratory Diseases, Mexico City, MexicoORCID Iconhttp://orcid.org/0000-0001-7289-1429
ORCID Icon,
Adriana Francisco-BalderasGraduate Studies Department, Escuela Superior de Medicina, Instituto Politécnico Nacional. Salvador Díaz Mirón esq. Plan de San Luis S/N, Miguel Hidalgo, Casco de Santo Tomas, Mexico City, MexicoORCID Iconhttp://orcid.org/0000-0001-8414-3436
ORCID Icon &
Yessica Zamudio-CuevasMusculoskeletal and Rheumatic Diseases Division, Synovial Fluid Laboratory, National Institute of Rehabilitation “Luis Guillermo Ibarra Ibarra”, Mexico City, MexicoCorrespondence[email protected]
ORCID Iconhttp://orcid.org/0000-0003-1751-3454
ORCID Icon show all
Pages 219-229 | Received 12 Feb 2018, Accepted 16 May 2018, Published online: 11 Jul 2018
 
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ABSTRACT

Background: The presence of genetic variants in uric acid (UA) transporters can be associated with hyperuricemia, and therefore with an increased risk of monosodium urate (MSU) crystal precipitation. The inflammatory process triggered by these crystals leads to cartilage damage, which, in turn, could promote knee osteoarthritis (KOA).

Objective: To determine whether genetic polymorphisms of the UA transporters and their interactions are associated with KOA.

Materials and Methods: Two hundred forty-three unrelated Mexican-mestizo individuals were recruited for this case-control study. Ninety-three of them were KOA patients but without gout, and one hundred and fifty healthy individuals with no symptoms or signs of KOA were recruited as controls. Forty-one single-nucleotide polymorphisms (SNPs) involved in the UA transporters were genotyped with OpenArray technology in a QuantStudio 12K flex-System with both cases and controls.

Results: After adjusting by age, gender, BMI, and ancestry, significant associations were found for eight SNPs: rs1260326 (GCKR), rs780093 (GCKR), rs17050272 (INHBB), rs1471633 (PDZK1), rs12129861 (PDZK1), rs7193778 (IGF1R), rs17786744 (STC1), and rs1106766 (R3HDM2). With respect to gene–gene interactions, the pairwise interactions of rs112129861 (PDZK1) and rs7193778 (IGF1R); rs17050272 (INHBB) and rs1106766 (R3HDM2); rs1106766 (R3HDM2) and rs780093 (GCKR); rs1260326 (GCKR) and rs17786744 (STC1); and rs17786744 (STC1) and rs1106766 (R3HDM2) make it possible to visualize the synergistic or antagonistic effect of their genotypes or alleles on KOA development.

Conclusions: Our preliminary results show that the common gene variants related to UA transport are associated with KOA in the Mexican population. Further studies must be carried out to corroborate it.

Declaration of interests

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

Supplementary material

Supplementary data can be accessed here.

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