Objetivo:

Las células del epitelio pigmentario retiniano tienden a la apoptosis en la distrofia macular de Stargardt (STGD). Anteriormente, los polimorfismos de un solo nucleótido (SNP) del gen del receptor Toll de tipo 4 (TLR4) se habían relacionado con la apoptosis y la inflamación. Por tanto, este estudio se realizó para investigar si los SNP del TLR4 están asociados con la STGD en un estudio familiar.

Métodos:

Se incluyeron 4 pacientes mexicanos consanguíneos con diagnóstico clínico de STGD (4 mujeres) y 12 familiares no afectados. Se utilizaron como control 109 sujetos (40 hombres y 69 mujeres; edad, 63.28 ± 7.93 años) sin enfermedades maculares ni antecedentes familiares. Los SNP rs4986790, rs1927911, rs12377632, rs2149356 y rs11536889 del gen TLR4 fueron genotipados usando un ensayo de discriminación alélica Taqman®.

Resultados:

La frecuencia del alelo menor rs4986790 (G) fue significativamente mayor en pacientes con STGD en comparación con los controles (25 vs. 1%; p = 0.0012). El genotipo portador del alelo menor rs4986790 (AG) fue más frecuente en los pacientes con STGD (50%) en comparación con sus familiares y controles (8 y 2.75%, respectivamente) de manera significativa (p = 0.0048). Las frecuencias alélicas y genotípicas de los SNP restantes no fueron significativas entre pacientes con STGD y controles (p > 0.5). Los familiares no afectados mostraron frecuencias alélicas y genotípicas similares a las encontradas en los controles.

Conclusión:

El alelo menor del SNP rs4986790 (G) y el genotipo portador (AG) se relacionaron con la enfermedad de Stargardt clínica. Curiosamente, el rs4986790 se ha descrito como un promotor de la apoptosis. Así, pues, este polimorfismo del gen TLR4 debe considerarse como un marcador en estudios futuros.

Purpose:

Retinal pigment epithelial cells exhibit a propensity for apoptosis in Stargardt macular dystrophy (STGD). Previously, single-nucleotide polymorphisms (SNPs) in the toll-like receptor 4 (TLR4) gene have been related to apoptosis and inflammatory response. Therefore, this study was undertaken to investigate whether TLR4 SNPs are associated with STGD in a family-based study.

Methods:

Four blood-related Mexican patients with a clinical diagnosis of STGD (4 women) and 12 of their unaffected relatives were included in the study. A total of 109 subjects (40 men and 69 women; age, 63.28 ± 7.93 years) without macular affections, family history, or inherited macular dystrophies were used as controls. SNPs rs4986790, rs1927911, rs12377632, rs2149356, and rs11536889 of the TLR4 gene were genotyped using a Taqman® Allelic Discrimination Assay.

Results:

The frequency of the minor allele of rs4986790 (G) was significantly higher in STGD patients compared to control subjects (25% vs. 1%, p = 0.0012). The genotype carrying the minor allele of rs4986790 (AG) was more frequent in STGD patients (50%) compared with their relatives and unrelated control subjects (8 and 2.75%, respectively), with statistical significance (p = 0.0048).The allele and genotype frequencies of the remaining SNPs were not significant between STGD patients and control subjects (p > 0.5). Unaffected relatives of STGD patients showed allele and genotype frequencies similar to those observed in control subjects.

Conclusion:

Minor alleles of the SNPs rs4986790 (G) and genotypes carrying it (AG) were related to clinical STGD in one family. Interestingly, rs4986790 has been described as a promoter of apoptosis. Therefore, this TLR4 gene polymorphism should be considered as a marker in future studies.

        · | |     · |     · ( pdf )