ESTUDIO DE VARIANTES MOLECULARES DE LOS GENES PTPN22, TNF Y VDR EN MADRES DE NIÑOS CON NEFRITIS LÚPICA Y SU ASOCIACIÓN COMO FACTORES DE RIESGO

La Nefritis Lupica (NL) es mas frecuente en mujeres. Se reconoce que madres con Lupus Eritematoso Sistemico (LES) confieren mayor riesgo al desarrollo de esta entidad en sus hijos. Esta transmision se debe a la impronta genomica y/o al genotipo materno sobre el desarrollo prenatal. En este estudio se identificaron variantes de los sistemas PTPN22, VDR y TNF, asociadas a NL pediatrica (NLp). Se investigo la asociacion de marcadores en 64 familias: 46 trios (Caso/Padre- Madre) y 18 duos (Caso/Madre). Se genotipificaron los SNPs rs2476601 [A/G] de PTPN22; rs361525 [A/G] y rs1800629 [A/G] de TNF; TaqI [rs731236 A/G], ApaI [rs7975232 A/C], BsmI [rs1544410 C/T] y FokI [rs2228570 A/G] de VDR mediante RT-PCR. Se estimo el efecto de la sobretransmision del alelo de riesgo de padres a hijos. Se estimo el efecto genetico de los SNPs sobre los ninos (R1 y R2) y tambien se estudiaron la influencia genetica materna (S1 y S2) y la impronta materna (Im). Se observo que el alelo A de rs2476601 en PTPN22 es sobretransmitido (p=0,028) en los ninos con nefritis lupica y se demostro que los ninos portadores de una copia del alelo A de rs2476601 presentan un riesgo (R1) de 0,20, mientras que dos copias del alelo (R2) lo incrementan a 1,71. Ademas, si la madre es portadora de dos copias del alelo A (S2), el riesgo aumenta a 2,5. La impronta genetica fue de 0,97 (p=0,002). Nuestro estudio describe la influencia materna de las variantes de PTPN22, TNF y VDR sobre ninos con NLp en familias colombianas. MATERNAL GENETIC VARIANTS IN PTPN22, TNF AND VDR AND THE RISK OF PEDIATRIC LUPUS NEPHRITIS ABSTRACT Lupus nephritis (LN) is more common in women. It is recognized that mothers with SLE confer increased risk to develop this entity to their children. This transmission is due the genomic imprint and/or maternal genotype on prenatal development. In this study, variants of PTPN22, TNF and VDR genes were identified and associated with pediatric LN (PLN). The association of markers was investigated in 64 families: 46 trios (case/Father-Mother) and 18 duos (case/ Mother). The SNPs rs2476601 [A/G] of PTPN22; the rs361525 [A/G], rs1800629 [A/G] from TNF and TaqI [rs731236 A/G], ApaI [rs7975232 A/C], BsmI [rs1544410 C/T] and FokI [rs2228570 A/G] of VDR gene were genotyped by RT-PCR. The effect of over-risk allele transmission from parents to children was estimated. The genetic effect of the SNPs on children (R1 and R2) was estimated and maternal genetic influence (S1 and S2) and maternal imprinting (Im). It was observed that the A allele of rs2476601 in PTPN22 is over-transmitted (p = 0,028) to PLN children, and that children carrying one copy of the allele of rs2476601 have a (R1) risk of 0,20; while two copies of allele (R2) increase it to 1,71. Also, if the mother carries two co- pies of allele A (S2), the risk become 2,5. DNA fingerprinting was 0,97 (p = 0,002). Our study describes maternal influence of the variants of PTPN22, TNF and VDR genes on children with PLN in colombian families.