Al Morshedy Salah, Elsaadany Hosam F, Ibrahim Hany E, Sherif Ashraf M, Farghaly Mohsen A A, Allah Mayy A N, Abouzeid Heba, Elashkar Shaimaa S A, Hamed Mohammed E, Fathy Manar M, Khalil Atef M, Noah Maha A, Hegab Mohamed S, Ahmed Ahmed R, Hashem Mustafa I A, Emam Ahmed A, Anany Heba G, Ibrahim Boshra R, Gawish Heba H, Nabil Rehab M, Fattah Lobna Abdel, Alsayed Salah F
Department of Pediatrics Department of Pediatrics, Faculty of Medicine, Cairo University Department of Pediatrics, Faculty of Medicine, Aswan University Department of Clinical pathology Department of Microbiology and Immunology Department of Internal Medicine, Faculty of Medicine, Zagazig University, Egypt.
Medicine (Baltimore). 2017 Mar;96(11):e6370. doi: 10.1097/MD.0000000000006370.
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-1β) 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-1β 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-1β 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-1β levels were measured by enzyme-linked immunosorbent assay (ELISA) method.The frequency of the IL-1β-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-1β 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-1β promoter and IL-1RA II/II genotype constitute risk factors for developing FS in Egyptian children.
热性惊厥是儿童期最常见的惊厥性疾病。在促炎细胞因子中，白细胞介素-1被定义为首个内源性致热原。我们设计本研究旨在调查白细胞介素-1β（IL-1β）基因启动子-31（C/T）和-511（C/T）位点的单核苷酸多态性（SNP）以及白细胞介素-1受体拮抗剂（IL-1RA）基因第2内含子的可变串联重复序列（VNTR）；确定这些多态性是否可能是埃及儿童热性惊厥易感性的标志物，并且我们还检测了血清IL-1β水平以评估其与这些多态性的关系。
这是一项病例对照研究，纳入了155例热性惊厥患者，并与年龄、性别、种族相匹配的155名健康对照者进行比较。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对IL-1β启动子-31（C/T）、-511（C/T）位点以及IL-1RA基因VNTR多态性进行基因分型，同时采用酶联免疫吸附测定（ELISA）法检测血清IL-1β水平。
与对照组相比，热性惊厥（FS）患者中IL-1β -511 TT基因型和该位点T等位基因的频率升高（TT基因型的优势比[OR]：3.96；95%置信区间[CI]：1.68 - 9.5；P = 0.001，T等位基因的OR：1.65；95% CI：1.18 - 2.3；P = 0.003）。FS患者中IL-1 RA II/II纯合变异型和IL-1 RA等位基因II的比例高于对照组（OR：4.02；95% CI：1.78 - 9.15；P = 0.001，OR：1.73；95% CI：1.24 - 2.4；P = 0.001）。我们发现，在散发病例中，IL-1 RA II/II基因型以及该位点的等位基因II与FS易感性之间存在显著正相关（IL-1 RA II/II基因型的OR：5.04；95% CI：2.1 - 12.5；P = 0.001）以及（等位基因II的OR：1.94；95% CI：1.3 - 2.8；P = 0.001）。与其他基因型和等位基因的携带者相比，IL-1RA II/II纯合变异型和等位基因II的携带者血清IL-1β水平显著更高。
我们首次证明，IL-1β启动子-511位点的T等位基因或TT基因型以及IL-1RA II/II基因型是埃及儿童发生FS的危险因素。
