Association of Interleukin 6 Gene Variant and Interleukin 6 level in Children with Congenital Heart Diseases: Single Center Case – Control Study

Background: Etiology of most congenital heart diseases (CHDs) is multifactorial, they include genetic and environmental factors. Interleukin-6 (IL-6) gene variant rs1800795 was reported to be associated with CHD among Chinese children.Aim of the work: to study the relationship of IL-6 rs1800795 gene variant and circulating serum IL-6 level in children with CHD.Subjects and Methods: This cross-sectional case control study included 100 Egyptian children (6 months to 16 years), of both sexes. Of them 50 patients with confirmed CHD (cyanotic and acyanotic) -free of other associated disease-, and 50 age and sex matched apparently healthy children. The rs1800795 variant of IL-6 gene was genotyped using TaqMan real-time polymerase chain reaction (PCR). The level of serum IL-6 was measured by ELISA for all participants.Results: The CHD comprised 25(50%) males and 25(50%) females with transposition of great arteries in 2(4%), ventricular septal defect in 10(20%), pulmonary stenosis in 6(12%), atrial septal defect in 10 (20%) and patent ductus arteriosus in 10 (20%), double outlet right ventricle in 1 (2%), Fallot tetralogy in 3 (6%), pulmonary atresia in 2 (4%), coarctation of aorta in 3 (6%) and partial anomalous pulmonary venous return in 1 (2%). Their mean age of 2.77 ± 1.81years, was comparable to the control group of 24 males and 26 females (p=0.841) and a mean age of 2.55 ± 1.43 years (p=0.511). Children with CHD exhibited significantly elevated serum IL-6 levels compared to healthy controls (338.68 ± 53.03 vs 136.9 ± 31.53 p < 0.001). An inverse correlation was identified between serum IL-6 titres and oxygen saturation (r= -0.300, p= 0.034). There was no correlation between IL-6 level and pulmonary hypertension (p=0.272), or heart failure (p=0.842). Il-6 gene variant rs 1800795 (cc, cg) was observed in 16(32%), 18(36%) with CHD respectively versus 8(16%) and 12(24%) of healthy control children (p=0.017). An increased trend of rs1800795 CC genotype and C allele was detected in the CHD patient group (p=0.017, p=0.001). IL-6 gene variant, and alleles were comparable between cyanotic and acyanotic heart diseases (p=0.925, p=0.317) respectively.Conclusion: Our studied Egyptian cohort of children with CHD had associated high serum IL-6 level and preponderance of IL-6 gene variant rs1800795 compared to the healthy matched control group. The IL-6 level negatively correlated with oxygen saturation. Longer prospective studies are needed to verify IL-6 role in disease susceptibility and progression.