Javier Fernández-Torres1,2, Gabriela Angélica Martínez-Nava3, Karina Martínez-Flores1, Roberto Sánchez-Sánchez4, Luis J Jara5, Yessica Zamudio-Cuevas6. 1. Laboratorio de Líquido Sinovial, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra Ibarra", Mexico City, Mexico. 2. Biology Department, Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico. 3. Laboratorio de Gerociencias, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra Ibarra", Mexico City, Mexico. 4. Unidad de Ingeniería de Tejidos, Terapia Celular y Medicina Regenerativa, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra Ibarra", Mexico City, Mexico. 5. Rheumatology Division, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra Ibarra", Mexico City, Mexico. 6. Laboratorio de Líquido Sinovial, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra Ibarra", Mexico City, Mexico. yesszamudio@gmail.com.
Abstract
BACKGROUND: HLA and NLRP3 play an important role in the development of various autoimmune and autoinflammatory diseases. Gout is an autoinflammatory disease associated with multiple genetic and environmental factors. The objective of the present study was to evaluate the interaction and association between genetic polymorphisms of HLA-B and the NLRP3 gene in Mexican patients with gout. METHODS AND RESULTS: Eighty-one patients with gout were included and compared with 95 healthy subjects. The polymorphisms rs4349859, rs116488202, rs2734583 and rs3099844 (within the HLA-B region) and rs3806268 and rs10754558 of the NLRP3 gene were genotyped using TaqMan probes in a Rotor-Gene device. The interactions were determined using the multifactorial dimensionality reduction (MDR) method, while the associations were determined through logistic regression models. The MDR analysis revealed significant interactions between the rs116488202 and rs10754558 polymorphisms with an entropy value of 4.31% (p < 0.0001). Significant risk associations were observed with rs4349859 and rs116488202 polymorphisms (p < 0.01); however, no significant associations were observed with the polymorphisms of the NLRP3 gene. CONCLUSIONS: The results suggest that HLA-B polymorphisms and their interaction with NLRP3 may contribute to the genetic susceptibility of gout.
BACKGROUND: HLA and NLRP3 play an important role in the development of various autoimmune and autoinflammatory diseases. Gout is an autoinflammatory disease associated with multiple genetic and environmental factors. The objective of the present study was to evaluate the interaction and association between genetic polymorphisms of HLA-B and the NLRP3 gene in Mexican patients with gout. METHODS AND RESULTS: Eighty-one patients with gout were included and compared with 95 healthy subjects. The polymorphisms rs4349859, rs116488202, rs2734583 and rs3099844 (within the HLA-B region) and rs3806268 and rs10754558 of the NLRP3 gene were genotyped using TaqMan probes in a Rotor-Gene device. The interactions were determined using the multifactorial dimensionality reduction (MDR) method, while the associations were determined through logistic regression models. The MDR analysis revealed significant interactions between the rs116488202 and rs10754558 polymorphisms with an entropy value of 4.31% (p < 0.0001). Significant risk associations were observed with rs4349859 and rs116488202 polymorphisms (p < 0.01); however, no significant associations were observed with the polymorphisms of the NLRP3 gene. CONCLUSIONS: The results suggest that HLA-B polymorphisms and their interaction with NLRP3 may contribute to the genetic susceptibility of gout.
Authors: Qiong Yang; Chao-Yu Guo; L Adrienne Cupples; Daniel Levy; Peter W F Wilson; Caroline S Fox Journal: Metabolism Date: 2005-11 Impact factor: 8.694
Authors: Yessica Zamudio-Cuevas; Gabriela Angélica Martínez-Nava; Karina Martínez-Flores; Lucio Ventura-Ríos; Janitzia Vazquez-Mellado; Pedro Rodríguez-Henríquez; Carlos Pineda; Rafael Franco-Cendejas; Carlos Alberto Lozada-Pérez; Javier Fernández-Torres Journal: Clin Rheumatol Date: 2021-02-17 Impact factor: 2.980