mtDNA Haplogroup A Enhances the Effect of Obesity on the Risk of Knee OA in a Mexican Population

[Abstract] To evaluate the influence of mitochondrial DNA haplogroups on the risk of knee OA in terms of their interaction with obesity, in a population from Mexico. Samples were obtained from (n = 353) knee OA patients (KL grade ≥ I) and (n = 364) healthy controls (KL grade = 0) from Mexico city and Torreon (Mexico). Both Caucasian and Amerindian mtDNA haplogroups were assigned by single base extension assay. A set of clinical and demographic variables, including obesity status, were considered to perform appropriate statistical approaches, including chi-square contingency tables, regression models and interaction analyses. To ensure the robustness of the predictive model, a statistical cross-validation strategy of B = 1000 iterations was used. All the analyses were performed using boot, GmAMisc and epiR package from R software v4.0.2 and SPSS software v24. The frequency distribution of the mtDNA haplogroups between OA patients and healthy controls for obese and non-obese groups showed the haplogroup A as significantly over-represented in knee OA patients within the obese group (OR 2.23; 95% CI 1.22-4.05; p-value = 0.008). The subsequent logistic regression analysis, including as covariate the interaction between obesity and mtDNA haplogroup A, supported the significant association of this interaction (OR 2.57; 95% CI 1.24-5.32; p-value = 0.011). The statistical cross-validation strategy confirmed the robustness of the regression model. The data presented here indicate a link between obesity in knee OA patients and mtDNA haplogroup A.This work is supported by Grants from Fondo de Investigación Sanitaria (PI17/00210, PI16/02124, PI20/00614, RETIC-RIER-RD16/0012/0002 and PRB3-ISCIII-PT17/0019/0014) integrated in the National Plan for Scientific Program, Development and Technological Innovation 2013–2016 and funded by the ISCIII-General Subdirection of Assessment and Promotion of Research-European Regional Development Fund (FEDER) “A way of making Europe” and Grant IN607A2017/11 from Xunta de Galicia. The authors further acknowledge AE CICA-INIBIC (ED431E 2018/03) for financial support. IRP is supported by Contrato Miguel Servet-II Fondo de Investigación Sanitaria (CPII17/00026) and AD-S is supported by Grant IN606A-2018/023 from Xunta de Galicia, Spain. The Biomedical Research Networking Center (CIBER) is an initiative from Instituto de Salud Carlos III (ISCIII)Xunta de Galicia; IN607A2017/11Xunta de Galicia; ED431E 2018/03Xunta de Galicia; IN606A-2018/02