Angiotensin-converting enzyme insertion/deletion gene polymorphism in Egyptian children with CAP: A case-control study.

BACKGROUND: Community-acquired pneumonia (CAP) is a major cause of childhood morbidity and mortality worldwide. The angiotensin-converting enzyme (ACE) gene is a potential candidate gene for CAP risk. OBJECTIVES: In this study, we aimed to investigate whether the ACE insertion/deletion (I/D) polymorphism (rs4340) could be a genetic marker for CAP susceptibility in Egyptian children, and we also measured the serum ACE level to assess its relation to such polymorphism. METHODS: This was a prospective case-control study included 300 patients with CAP, and 300 age, gender, and ethnicity matched healthy controls. The ACE I/D polymorphism (rs4340) at intron 16 was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while the serum ACE levels were measured by ELISA. RESULTS: Compared to the controls subjects, the frequencies of the ACE DD genotype and D allele were overrepresented in patients with CAP (OR = 3.05; [95%CI: 2.14-4.35] for the DD genotype; P < 0.001) and (OR: 1.8; [95%CI: 1.42-2.29]; for the D allele; P < 0.01, respectively). Patients with the DD genotype had significantly higher mean serum ACE levels (45.6 ± 11.4 U/L) compared to those with ID genotype (36.5 ± 8.3 U/L) and II genotype (21.6 ± 5.7 U/L); P < 0.01, respectively. CONCLUSION: The ACE I/D polymorphism (rs4340) may contribute to the genetic susceptibility of CAP in Egyptian children. The ACE D allele and DD genotype were associated with higher serum ACE levels among studied CAP patients.

Interleukin-1ß and interleukin-1receptor antagonist polymorphisms in Egyptian children with febrile seizures: A case-control study.

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 -31 (C/T), and -511 (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 -31 (C/T), -511 (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; P = 0.001 for the TT genotype and OR: 1.65; 95% CI: 1.18-2.3; P = 0.003 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; P = 0.001and OR: 1.73; 95% CI: 1.24-2.4; P = 0.001, 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; P = 0.001) and (OR: 1.94; 95% CI: 1.3-2.8 for the allele II; P = 0.001, 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.