Association of interleukin-17A gene polymorphisms and susceptibility to systemic lupus erythematosus in Egyptian children and adolescents: a multi-centre study.

BACKGROUND: Recently, the interleukin-17A (IL-17A) gene has emerged as a potential candidate gene for autoimmune disorders, including systemic lupus erythematosus (SLE). OBJECTIVES: This study aimed to investigate whether IL-17A polymorphisms at rs2275913 G/A, rs8193036 C/T and rs3748067 C/T could be susceptibility markers for juvenile-onset SLE (JSLE) and lupus nephritis (LN) in Egyptian children and adolescents. METHODS: In this multi-centre study, we genotyped 320 patients diagnosed with JSLE and 320 matched control children for three IL-17A polymorphisms at rs2275913 G/A, rs8193036 C/T and rs3748067 C/T using TaqMan probe-based real-time polymerase chain reaction. Meanwhile, IL-17A serum levels were assessed using ELISA. RESULTS: The IL-17 rs2275913 A/A genotype and A allele were more represented in JSLE patients compared to the control group (21% vs. 7%, odds ratio (OR) = 3.8, 95% confidence interval (CI) 1.78-5.5, p = 0.001, pBonf = 0.003 for the A/A genotype; 37% vs. 29%, OR = 1.4, 95% CI 1.11-1.8, p = 0.003, pBonf = 0.009 for the A allele. No significant difference was found for IL-17 rs8193036 and rs3748067 single nucleotide polymorphisms (SNPs) in genotype distribution or allele frequencies (p>0.05). Patients carrying the IL-17 rs2275913 A/A genotype and A allele were more likely to develop LN (OR = 5.64, 95% CI 2.39-13.77, pBonf = 0.001 for the A/A genotype; OR = 2.73, 95% CI 1.84-4.07, pBonf = 0.02 for the A allele). CONCLUSION: The IL-17 rs2275913 A allele and A/A genotype were associated with high IL-17 serum levels and may contribute to susceptibility to JSLE and the development of LN in Egyptian children and adolescents. However, no significant association was evident between the studied IL-17A SNPs and other clinical phenotypes, disease activity scores or laboratory profile of JSLE.

Association of vitamin D receptor gene FokI polymorphism and susceptibility to CAP in Egyptian children: a multicenter study.

BACKGROUND: Community-acquired pneumonia (CAP) is the leading cause of child deaths around the world. Recently, the vitamin D receptor (VDR) gene has emerged as a susceptibility gene for CAP. OBJECTIVES: To evaluate the association of the VDR gene Fok I polymorphism with susceptibility to CAP in Egyptian children. METHODS: This was a multicenter case-control study of 300 patients diagnosed with CAP, and 300 well-matched healthy control children. The VDR Fok I (rs2228570) polymorphism was genotyped by PCR-restriction fragment length polymorphism (RFLP), meanwhile serum 25-hydroxy vitamin D (25D) level was assessed using ELISA method. RESULTS: The frequencies of the VDR FF genotype and F allele were more common in patients with CAP than in our control group (OR = 3.6; (95% CI: 1.9-6.7) for the FF genotype; P = 0.001) and (OR: 1.8; (95% CI: 1.4-2.3) for the F allele; P = 0.01). Patients carrying the VDR FF genotype had lower serum (25D) level (mean; 14.8 ± 3.6 ng/ml) than Ff genotype (20.6 ± 4.5 ng/ml) and the ff genotype (24.5 ± 3.7 ng/ml); P < 0.01. CONCLUSION: The VDR gene Fok I (rs2228570) polymorphism confers susceptibility to CAP in Egyptian children.

Ficolin-1 gene (FCN1) -144 C/A polymorphism is associated with adverse outcome of severe pneumonia in the under-five Egyptian children: A multicenter study.

BACKGROUND: Pneumonia is the foremost cause of child death worldwide. M-ficolin is encoded by the FCN1 gene and represents a novel link between innate and adaptive immunity. OBJECTIVES: To investigate the FCN1 -144 C/A (rs10117466) polymorphism as a potential marker for pneumonia severity and adverse outcome namely complications or mortality in the under-five Egyptian children. METHODS: This was a prospective multicenter study that included 620 children hospitalized with World Health Organization-defined severe pneumonia and 620 matched healthy control children. Polymorphism rs10117466 of the FCN1 gene promoter was analyzed by PCR-SSP, while serum M-ficolin levels were assessed by ELISA. RESULTS: The FCN1 A/A genotype and A allele at the -144 position were more frequently observed in patients compared to the control children (43.4% vs 27.6%; odds ratio [OR]: 1.62; [95% confidence interval {CI}: 1.18-2.2]; for the A/A genotype) and (60.8% vs 52.5%; OR: 1.4; [95% CI: 1.19-1.65]; for the A allele); P < .01. The FCN1 -144 A/A homozygous patients had significantly higher serum M-ficolin concentrations (mean: 1844 ± 396 ng/mL) compared with those carrying the C/C or C/A genotype (mean: 857 ± 278 and 1073 ± 323 ng/mL, respectively; P = .002). FCN1 -144 A/A genotype was an independent risk factor for adverse outcomes in children with severe pneumonia (adjusted OR = 4.85, [95% CI: 2.96-10.25]; P = .01). CONCLUSION: The FCN1 A/A genotype at the -144 position was associated with high M-ficolin serum levels and possibly contributes to enhanced inflammatory response resulting in the adverse outcome of pneumonia in the under-five Egyptian children.

Interleukin-4 -590C/T gene polymorphism in Egyptian children with acute lower respiratory infection: A multicenter study.

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.