Evaluation of variants in IL6R, TLR3, and DC-SIGN genes associated with dengue in a sampled Colombian population / Evaluación de las variantes en los genes IL6R, TLR3 y DC-SIGN asociadas con dengue en una muestra de población colombiana

Abstract Introduction: Host genetics is recognized as an influential factor for the development of dengue disease. Objective: This study evaluated the association of dengue with the polymorphisms rs8192284 for gene IL6R, rs3775290 for TLR3, and rs7248637 for DC-SIGN. Materials and methods: Of the 292 surveyed subjects, 191 were confirmed for dengue fever and the remaining 101 were included as controls. The genotypes were resolved using polymerase chain reaction and restriction fragment length polymorphism (PCR- RFLP). In an attempt to determine the risk (Odds Ratio) of suffering dengue fever, data were analyzed using chi-square for alleles and logistic regression for both genotypes and allelic combinations. Confidence intervals were set to 95% for all tests regardless of the adjustment by either self-identification or ancestry. Results: For Afro-Colombians, the allele rs8192284 C offered protection against dengue [OR=0.425,(0.204-0.887), p=0.020]. The alleles rs7248637 A and rs3775290 A posed, respectively, an increased risk of dengue for Afro-Colombians [OR=2.389, (1.170-4.879), p=0.015] and Mestizos [OR=2.329, (1.283-4.226), p=0.005]. The reproducibility for rs8192284 C/C [OR=2.45, (1.05-5.76), p=0.013] remained after adjustment by Amerindian ancestry [OR=2.52, (1.04-6.09), p=0.013]. The reproducibility for rs3775290 A/A [OR=2.48, (1.09-5.65), p=0.033] remained after adjustment by European [OR=2.34, (1.02-5.35), p=0.048], Amerindian [OR=2.49, (1.09-5.66), p=0.035], and African ancestry [OR=2.37, (1.04-5.41), p=0.046]. Finally, the association of dengue fever with the allelic combination CAG [OR=2.07, (1.06-4.05), p=0.033] remained after adjustment by Amerindian ancestry [OR=2.16, (1.09-4.28), p=0.028]. Conclusions: Polymorphisms rs8192284 for IL6R, rs3775290 for TLR3, and rs7248637 for DC-SIGN were associated with the susceptibility to suffer dengue fever in the sampled Colombian population.

Resumen Introducción. La genética del huésped se reconoce como un factor que influye en el desarrollo del dengue. Objetivo. Este estudio evaluó la asociación del dengue con los polimorfismos rs8192284 del gen IL6R, rs3775290 del TLR3 y rs7248637 del DC-SIGN. Materiales y métodos. De los 292 sujetos encuestados, en 191 se confirmó la presencia de fiebre por dengue y los restantes 101 se incluyeron como controles. Los genotipos se resolvieron mediante reacción en cadena de la polimerasa y polimorfismos en la longitud de los fragmentos de restricción (PCR-RFLP). En un intento por determinar el riesgo de sufrir dengue, los datos se analizaron mediante la prueba de ji al cuadrado para los alelos y la regresión logística para los genotipos y las combinaciones alélicas. Los intervalos de confianza se calcularon a 95 % para todas las pruebas independientemente ajustadas por autoidentificación o componente genético ancestral. Resultados. En los afrocolombianos, el alelo C rs8192284 ofreció protección contra el dengue (OR=0,425; 0,204-0,887, p=0,020). Los alelos A rs7248637 y Ars3775290 plantearon un mayor riesgo de dengue para los afrocolombianos (OR=2,389; 1,170- 4,879; p=0,015) y los mestizos (OR=2,329; 1,283-4,226: p=0,005), respectivamente. La reproducibilidad para rs8192284 C/C (OR=2,45; 1,05-5,76; p=0,013) permaneció después del ajuste por el componente genético ancestral amerindio (OR=2,52; 1,04- 6,09; p=0,013). La reproducibilidad del rs3775290 A/A (OR=2,48; 1,09-5,65; p=0,033) permaneció después del ajuste por el componente europeo (OR=2,34; 1,02-5,35; p=0,048), el amerindio (OR=2,49; 1,09- 5,66; p=0,035), y el africano (OR=2,37; 1,04- 5,41; p=0,046). Por último, la asociación del dengue con la combinación alélica CAG (OR=2,07; 1,06-4,05; p=0,033) permaneció después del ajuste por el componente genético amerindio (OR=2,16; 1,09-4,28;p=0,028). Conclusión. Los polimorfismos rs8192284 en IL6R, rs3775290 en TLR3 y rs7248637 en DC-SIGN, se asociaron con la propensión a sufrir dengue en una muestra de población colombiana.

Interleukin-6 Receptor Polymorphisms Contribute to the Neurological Status of Korean Patients with Ischemic Stroke

To investigate the contribution of the interleukin-6 receptor (IL-6R) gene single nucleotide polymorphisms (SNPs) to the neurological status of Korean patients with ischemic stroke (IS), two SNPs of the IL-6R gene (rs4845617, 5 UTR; rs2228144, Ala31Ala) were selected. IS patients were classified into clinical phenotypes according to two well-defined scores: the National Institutes of Health Stroke Survey (NIHSS) and the Modified Barthel Index scores. There were 121 IS patients and 291 control subjects. The SNP rs4845617 significantly contributed to the neurological status of patients with IS (P = 0.011 in codominant model 2, P = 0.006 in recessive model, and P = 0.008 in log-additive model). Allele frequencies of rs4845617 and rs2228144 demonstrated no significant difference in IS patients and controls. The AG and GG haplotypes differed between the NIHSS 1 (NIHSS scores or = 6) group in patients with IS (P = 0.014, P = 0.0024). These results suggest that rs4845617 of the IL-6R gene is associated with the neurologic status of Korean patients with IS.