Epistasis Between Two Gene Variants of Leptin and Vascular Endothelial Growth Factor Genes in the Development of Primary Knee Osteoarthritis.

BACKGROUND

The association of leptin () and vascular endothelial growth factor A () genes with the susceptibility to knee osteoarthritis (OA) has been analyzed; however, the epistasis between them has not been investigated.

OBJECTIVE

The objective of the study was to analyze the association of and variants and their interaction with primary knee OA in a Mexican Mestizo population.

METHODS

A case-control study was developed. Cases were ≥40 years, BMI ≤27 kg/m, with primary knee OA and radiologic Grade ≥2. Controls were participants with no knee OA and a radiologic Grade < 2. The rs2167270 of and rs2010963 of were genotyped. Genotypic association was tested under codominant, dominant, and recessive models. Uni- and multi-variate analyses were developed through non-conditional logistic regression. The multifactor dimensionality reduction algorithm was developed to detect epistasis.

RESULTS

Participants comprised 103 cases and 179 controls. Allelic and genotypic distributions did not show differences between the groups. Notwithstanding, a statistically significant interaction was observed between the and genes (p = 0.02) with a testing accuracy of 0.5199 and cross-validation consistency of 10/10. This interaction model confers an increased risk to knee OA (OR [95% CI] = 1.8 [1.1-2.9]).

CONCLUSION

Interaction between and is related with genetic susceptibility to developing primary knee OA.