title: Association of IL-10 gene polymorphisms and susceptibility to Juvenile Idiopathic Arthritis in Egyptian children and adolescents: a case-control study.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Zagazig University, 13 Omar Bin Elkhattab St, Al Qawmia, Zagazig City, AlSharqia Governorate, Egypt. fzeidan22@yahoo.com.
authors.forename: Manar M
authors.initials: MM
authors.lastname: Fathy
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Zagazig University, 13 Omar Bin Elkhattab St, Al Qawmia, Zagazig City, AlSharqia Governorate, Egypt.
authors.forename: Hosam F
authors.initials: HF
authors.lastname: Elsaadany
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Zagazig University, 13 Omar Bin Elkhattab St, Al Qawmia, Zagazig City, AlSharqia Governorate, Egypt.
authors.forename: Yasser F
authors.initials: YF
authors.lastname: Ali
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Aswan University, Aswan, Egypt.
authors.forename: Mohsen A A
authors.initials: MA
authors.lastname: Farghaly
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Zagazig University, 13 Omar Bin Elkhattab St, Al Qawmia, Zagazig City, AlSharqia Governorate, Egypt.
authors.forename: Mohammed E
authors.initials: ME
authors.lastname: Hamed
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Zagazig University, 13 Omar Bin Elkhattab St, Al Qawmia, Zagazig City, AlSharqia Governorate, Egypt.
authors.forename: Hany E
authors.initials: HE
authors.lastname: Ibrahim
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Zagazig University, 13 Omar Bin Elkhattab St, Al Qawmia, Zagazig City, AlSharqia Governorate, Egypt.
authors.forename: Maha A
authors.initials: MA
authors.lastname: Noah
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Zagazig University, 13 Omar Bin Elkhattab St, Al Qawmia, Zagazig City, AlSharqia Governorate, Egypt.
authors.forename: Mayy A N
authors.initials: MA
authors.lastname: Allah
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Zagazig University, 13 Omar Bin Elkhattab St, Al Qawmia, Zagazig City, AlSharqia Governorate, Egypt.
authors.forename: Shaimaa S A
authors.initials: SS
authors.lastname: Elashkar
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Zagazig University, 13 Omar Bin Elkhattab St, Al Qawmia, Zagazig City, AlSharqia Governorate, Egypt.
authors.forename: Nasser I
authors.initials: NI
authors.lastname: Abdelsalam
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Zagazig University, 13 Omar Bin Elkhattab St, Al Qawmia, Zagazig City, AlSharqia Governorate, Egypt.
authors.forename: Hind M
authors.initials: HM
authors.lastname: Abdelrahman
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Zagazig University, 13 Omar Bin Elkhattab St, Al Qawmia, Zagazig City, AlSharqia Governorate, Egypt.
authors.forename: Ahmed R
authors.initials: AR
authors.lastname: Ahmed
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Zagazig University, 13 Omar Bin Elkhattab St, Al Qawmia, Zagazig City, AlSharqia Governorate, Egypt.
authors.forename: Heba G
authors.initials: HG
authors.lastname: Anany
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Zagazig University, 13 Omar Bin Elkhattab St, Al Qawmia, Zagazig City, AlSharqia Governorate, Egypt.
authors.forename: Sanaa M
authors.initials: SM
authors.lastname: Ismail
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Zagazig University, 13 Omar Bin Elkhattab St, Al Qawmia, Zagazig City, AlSharqia Governorate, Egypt.
authors.forename: Boshra R
authors.initials: BR
authors.lastname: Ibrahim
authors.affiliation: Department of Clinical Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
authors.forename: Nashwa M
authors.initials: NM
authors.lastname: Al Azizi
authors.affiliation: Department of Clinical Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
authors.forename: Heba H
authors.initials: HH
authors.lastname: Gawish
authors.affiliation: Department of Clinical Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
authors.forename: Ghada M
authors.initials: GM
authors.lastname: Al-Akad
authors.affiliation: Department of Clinical Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
authors.forename: Rehab M
authors.initials: RM
authors.lastname: Nabil
authors.affiliation: Department of Rheumatology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
authors.forename: Dalia S
authors.initials: DS
authors.lastname: Fahmy
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
authors.forename: Salah F
authors.initials: SF
authors.lastname: Alsayed
mesh_terms: D000293:Adolescent; D000483:Alleles; D001171:Arthritis, Juvenile / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D004534:Egypt; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; C508609:IL10 protein, human; D016753:Interleukin-10
keywords: Cytokines; Gene polymorphisms; Interleukin-10; Juvenile idiopathic arthritis