Asociación de variantes polimórficas de los sistemas PTPN22, TNF y VDR en niños con nefritis lúpica: un estudio en tríos de familias colombianas
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Fecha
2017
Autores
Garavito, Gloria
Egea, Eduardo
Fang, Luis
Malagón, Clara
Olmos, Carlos
González, Luz
Guarnizo, Pilar
Aroca, Gustavo
López, Guillermo
Iglesias, Antonio
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Editor
Instituto Nacional de Salud
Resumen
Introducción. El lupus eritematoso sistémico es una enfermedad autoinmune cuya gravedad varía según la raza, género y edad de aparición. Esta disparidad también se observa en los marcadores genéticos asociados con la enfermedad presentes en los genes PTPN22, VDR y TNF. La estratificación genética que presentan las diferentes poblaciones en el mundo puede estar influyendo dicha variabilidad.
Objetivo. Analizar la asociación y heredabilidad de variantes genéticas de los genes PTPN22, VDR y TNF con nefritis lúpica pediátrica (NLp) en familias colombianas.
Materiales y métodos. Se realizó un estudio basado en familias con 46 tríos (caso/padre y madre). Se genotipificaron las variantes rs2476601 de PTPN22; rs361525 y rs1800629 de TNF; TaqI [rs731236], ApaI [rs7975232], BsmI [rs1544410] y FokI [rs2228570] de VDR mediante qPCR. Se estimó el efecto de la sobretransmisión del alelo de riesgo de padres a hijos y el desequilibrio de ligamiento de los loci VDR y TNF.
Resultados. Se observó que el alelo A de rs2476601 en PTPN22 se distribuyó en el 8,69 % [n=16] de los padres mientras que en los casos es de 19,5 % [n=18] al igual que es sobretransmitido de padres a hijos 17 veces más con relación al alelo G (p=0,028). Los polimorfismos de TNF y VDR no se mostraron en desequilibrio de transmisión. Las variantes TaqI, ApaI y BsmI del VDR se mostraron en desequilibrio de ligamiento.
Conclusión. Estos hallazgos muestran una asociación del polimorfismo rs2476601 de PTPN22 con NLp debido a su sobretransmisión en el grupo de familias estudiadas.
Introduction: Systemic lupus erythematosus is an autoimmune disease with severity that varies according to race, gender and age of onset. This variation is also observed in genetic markers associated with the disease, present in the PTPN22, VDR, and TNF genes. It is possible that the genetic stratification observed in different populations in the world can be influencing this variability. Objective: To analyze the association and heritability of PTPN22, VDR and TNF gene variants with pediatric lupus nephritis (PLN) in Colombian families. Materials and methods: a study based on 46 trios (Case / parents) was performed. Genotyping by qPCR of variants of rs2476601 in PTPN22; rs361525 and rs1800629 in TNF; TaqI [rs731236], ApaI [rs7975232] BsmI [rs1544410] and FokI [rs2228570] in VDR was performed. The effect of the risk of allele over-transmission through families and linkage disequilibrium of VDR and TNF loci was estimated. Results: We observed that the A allele of rs2476601 in PTPN22 was distributed in 8.69% [n = 16] parents, and increased to 19.5% [n = 18] in cases. Over-transmission of this allele was also observed from parents to offspring 17 times relative to the G allele (p = 0.028). TNF and VDR polymorphisms were not overtransmitted. SNPs TaqI, ApaI y BsmI in VDR showed linkage disequilibrium. Conclusion: These findings seem to demonstrate an association of rs2476601 in PTPN22 with PLN due to its overtransmission in the group of families studied.
Introduction: Systemic lupus erythematosus is an autoimmune disease with severity that varies according to race, gender and age of onset. This variation is also observed in genetic markers associated with the disease, present in the PTPN22, VDR, and TNF genes. It is possible that the genetic stratification observed in different populations in the world can be influencing this variability. Objective: To analyze the association and heritability of PTPN22, VDR and TNF gene variants with pediatric lupus nephritis (PLN) in Colombian families. Materials and methods: a study based on 46 trios (Case / parents) was performed. Genotyping by qPCR of variants of rs2476601 in PTPN22; rs361525 and rs1800629 in TNF; TaqI [rs731236], ApaI [rs7975232] BsmI [rs1544410] and FokI [rs2228570] in VDR was performed. The effect of the risk of allele over-transmission through families and linkage disequilibrium of VDR and TNF loci was estimated. Results: We observed that the A allele of rs2476601 in PTPN22 was distributed in 8.69% [n = 16] parents, and increased to 19.5% [n = 18] in cases. Over-transmission of this allele was also observed from parents to offspring 17 times relative to the G allele (p = 0.028). TNF and VDR polymorphisms were not overtransmitted. SNPs TaqI, ApaI y BsmI in VDR showed linkage disequilibrium. Conclusion: These findings seem to demonstrate an association of rs2476601 in PTPN22 with PLN due to its overtransmission in the group of families studied.
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Palabras clave
Lupus eritematoso sistémico, Nefritis lúpica pediátrica, Desequilibrio de ligamiento, Estudios de asociación genética, Lupus erythematosus, systemic, Linkage disequilibrium, Genetic association studies