RESUMEN
BACKGROUND: Acute lower respiratory infection (ALRI) is the leading cause of child mortality, especially in the developing world. Polymorphisms in the interleukin 4 (IL-4) gene have been linked to a variety of human diseases. OBJECTIVES: To investigate whether the IL-4 -590C/T (rs2243250) polymorphism could be a genetic marker for susceptibility to ALRIs in young Egyptian children. METHODS: This was a multicenter study conducted on 480 children diagnosed with pneumonia or bronchiolitis, and 480 well-matched healthy control children. Using PCR-RFLP analysis, we genotyped a -590C/T (rs2243250) single nucleotide polymorphism of the IL-4 gene promoter, meanwhile the serum IL-4concentration was measured by ELISA. RESULTS: The frequency of the IL-4 -590 T/T genotype and T allele were overrepresented in patients with ALRIs in comparison to the control group (OR = 2.0; [95% confidence interval [CI]: 1.38-2.96]; for the T/T genotype) and (OR: 1.3; [95%CI: 1.07-1.56]; for the T allele; P < 0.01). The IL-4 -590 T/T genotype was associated with significantly higher mean serum IL-4 concentration (58.7 ± 13.4 pg/mL) compared to the C/T genotype (47.6 ± 11 pg/mL) and the C/C genotype (34.8 ± 9.6 pg/mL); P < 0.01. CONCLUSION: The IL-4 -590C/T (rs2243250) polymorphism may contribute to susceptibility to ALRIs in young Egyptian children.
Asunto(s)
Bronquiolitis/genética , Predisposición Genética a la Enfermedad , Interleucina-4/genética , Neumonía/genética , Infecciones del Sistema Respiratorio/genética , Alelos , Bronquiolitis/sangre , Preescolar , Egipto , Femenino , Genotipo , Humanos , Lactante , Interleucina-4/sangre , Masculino , Neumonía/sangre , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Infecciones del Sistema Respiratorio/sangreRESUMEN
Febrile seizure is the most common seizure disorder of childhood. Of the pro-inflammatory cytokines, interleukin-1 is defined as the first endogenous pyrogen.We designed this study to investigate single-nucleotide polymorphisms (SNPs) situated at positions -31â(C/T), and -511â(C/T) of interleukin-1beta (IL-1ß) gene promoter and interleukin-1receptor antagonist (IL-1RA) gene variable number of tandem repeats in intron 2 (VNTR); to determine whether these polymorphisms could be a marker of susceptibility to febrile seizures in Egyptian children and we also measured the serum level of IL-1ß to assess its relation to such polymorphisms.This was a case-control study included 155 patients with febrile seizure, and matched with age, sex, ethnicity 155 healthy control subjects. IL-1ß promoter at positions -31â(C/T), -511â(C/T), and IL-1RA gene VNTR polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while the serum IL-1ß levels were measured by enzyme-linked immunosorbent assay (ELISA) method.The frequency of the IL-1ß-511 TT genotype and T allele at the same position were observed to be increased in patients with febrile seizures (FS) compared with the control group (odds ratio [OR]: 3.96; 95% confidence interval [CI]: 1.68-9.5; Pâ=â0.001 for the TT genotype and OR: 1.65; 95% CI: 1.18-2.3; Pâ=â0.003 for the T allele, respectively). The IL-1 RA II/II homozygous variant and IL-1 RA allele II were overrepresented in patients with FS than control group (OR: 4.02; 95% CI: 1.78-9.15; Pâ=â0.001and OR: 1.73; 95% CI: 1.24-2.4; Pâ=â0.001, respectively). We found a significant positive association between the IL-1 RA II/II genotype and susceptibility to FS in sporadic cases as did allele II at the same position (OR: 5.04; 95% CI: 2.1-12.5 for the IL-1 RA II/II genotype; Pâ=â0.001) and (OR: 1.94; 95% CI: 1.3-2.8 for the allele II; Pâ=â0.001, respectively). Carriers of the IL-1RA II/II homozygous variant and allele II had significantly higher serum levels of IL-1ß compared with those with other genotypes and alleles.We demonstrate for the first time that the presence of a T allele or TT genotype at -511 of IL-1ß promoter and IL-1RA II/II genotype constitute risk factors for developing FS in Egyptian children.
Asunto(s)
Proteína Antagonista del Receptor de Interleucina 1/genética , Interleucina-1beta/genética , Convulsiones Febriles/genética , Alelos , Estudios de Casos y Controles , Niño , Preescolar , Egipto/epidemiología , Femenino , Genotipo , Humanos , Lactante , Masculino , Oportunidad Relativa , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas/genéticaRESUMEN
BACKGROUND: Juvenile Idiopathic Arthritis (JIA) is the most common chronic arthritis in children worldwide. Among anti-inflammatory cytokines, interleukin-10 (IL-10) is a key immunosuppressive cytokine involved in the pathogenesis of JIA. To date, only a few studies concerned the association of interleukin-10 gene polymorphisms with JIA. In this study, we aimed to investigate 3 cytokine single-nucleotide polymorphisms situated at positions -1082(G/A), -819(C/T), and -592(C/A) in the promoter region of the IL-10 gene to determine whether this polymorphism could be a marker of susceptibility to JIA in Egyptian children and adolescents. We also measured the serum level of IL-10 to assess its relation to such polymorphism. METHODS: This was a case-control study included 100 patients diagnosed with JIA, and matched with age, gender, ethnicity 100 healthy control subjects. Interleukin-10 -1082(G/A), -819(C/T), and -592(C/A) polymorphisms were genotyped by amplification refractory mutation system- polymerase chain reaction (ARMS)-PCR methodology, while the serum IL10 levels were measured by ELISA method. RESULTS: Compared to the controls subjects, the frequency of IL-10- AA genotype and A allele at the -1082 position were overrepresented in patients with JIA (OR = 2.7; 95% CI: 1.1-6.4 for the AA genotype; P <0.05 and OR: 1.5; 95% CI: 1.03-2.3 for the A allele; P <0.05 respectively). On the other hand, no significant differences were found between the 2 groups in the genotype or allele frequencies for the -819 and -592 positions. Of note, we found a significant positive association between the IL-10 (-1082) AA genotype and susceptibility to polyarticular JIA (OR: 4.3; 95% CI: 1.5-12.7; P <0.01). We observed that patients with the IL-10 (-1082) AA genotype had significantly lower serum IL-10 levels (2.3 ± 0.9 pg/ml) compared to those with AG genotype (7.6 ± 1.5 pg/ml) and GG genotype (9.5 ± 1.2 pg/ml); P < 0.01, respectively. CONCLUSION: We demonstrate for the first time, to the best of our knowledge, that the presence of an A allele or AA gene variant at the -1082 position of the promoter region of the interleukin-10 gene may constitute risk factors for developing JIA in Egyptian children and adolescents. Moreover, we observed a significant positive association between the IL10 -1082 AA gene variant and susceptibility to polyarticular JIA.