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Association of IL-4 (intron 3) and IL-10 (-1082) gene polymorphisms with risk of mitral valve disease in children with rheumatic heart disease

Published online by Cambridge University Press:  28 October 2015

Sherif M. Yousry*
Affiliation:
Department of Clinical Pathology, Cairo University, Giza, Egypt
Yasser Sedky
Affiliation:
Department of Pediatrics, Cairo University, Giza, Egypt
Alaa Sobieh
Affiliation:
Department of Pediatrics, Cairo University, Giza, Egypt
*
Correspondence to: S. M. Yousry, Department of Clinical Pathology, Cairo University, 132 Al Bahr Al Azam Street, Giza 11221, Egypt. Tel: (+2)0235736727; Fax: (+2)0235700977; E-mail: [email protected]

Abstract

Aim

Rheumatic heart disease is an inflammatory disease of cardiac tissue. The underlying pathogenic mechanisms highlight a complex interplay of immunological, genetic, and environmental factors. The aim of the present study was to investigate whether IL-4 (intron 3) and IL-10 (-1082) gene polymorphisms could be associated with susceptibility and/or severity of rheumatic heart disease among patients from the Egyptian population.

Materials and methods

A cohort of 140 Egyptian children with rheumatic heart disease and 100 healthy controls were enrolled in this case–control study. Genotyping for IL-4 (intron 3) and IL-10 (-1082) gene polymorphisms was carried out for all patients using a polymerase chain reaction-based analysis.

Results

No significant difference in the distribution of genotypes and allelic frequencies between rheumatic heart disease cases and controls for IL-4 (intron 3) (p=0.17; OR 1.07, 95% CI 0.82–3.74) and IL-10 (-1082) (p=0.49; OR 1.03, 95% CI 0.65–2.71) gene polymorphisms was observed. Further categorisation of patients into mitral valve disease and combined valve disease subgroups showed that cases with mitral valve disease have significantly higher frequency of the RP2 allele of IL-4 (intron 3) (p=0.03; OR 2.98, 95% CI 1.93–6.15) and the G allele of IL-10 (-1082) (p=0.04; OR 2.14, 95% CI 1.62–4.95) when compared with controls.

Discussion

Our study shows that IL-4 (intron 3) and IL-10 (-1082) gene polymorphisms are not significantly associated with susceptibility to rheumatic heart disease, but they might play a role in the pathogenesis of patients with mitral valve disease.

Type
Original Articles
Copyright
© Cambridge University Press 2015 

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References

1. Guilherme, L, Köhler, KF, Postol, E, Kalil, J. Genes, autoimmunity and pathogenesis of rheumatic heart disease. Ann Pediatr Cardiol 2011; 4: 1321.CrossRefGoogle ScholarPubMed
2. Stanevicha, V, Eglite, J, Sochnevs, A, Gardovska, D, Zavadska, D, Shantere, R. HLA class II associations with rheumatic heart disease among clinically homogeneous patients in children in Latvia. Arthritis Res Ther 2003; 5: R340R346.CrossRefGoogle ScholarPubMed
3. Harrington, Z, Visvanathan, K, Skinner, NA, Curtis, N, Currie, BJ, Carapetis, JR. B-cell antigen D8/17 is a marker of rheumatic fever susceptibility in Aboriginal Australians and can be tested in remote settings. Med J Aust 2006; 184: 507510.CrossRefGoogle ScholarPubMed
4. Carapetis, JR, Brown, A, Wilson, NJ, Edwards, KN. An Australian guideline for rheumatic fever and rheumatic heart disease: an abridged outline. Med J Aust 2007; 186: 581586.CrossRefGoogle ScholarPubMed
5. Ayoub, EM, Nelson, B, Shulman, ST, et al. Group A streptococcal antibodies in subjects with or without rheumatic fever in areas with high or low incidences of rheumatic fever. Clin Diagn Lab Immunol 2003; 10: 886890.Google ScholarPubMed
6. Elahi, MM, Asotra, K, Matata, BM, Mastana, SS. Tumor necrosis factor alpha – 308 gene locus promoter polymorphism: an analysis of association with health and disease. Biochim Biophys Acta Mol Basis Dis 2009; 1792: 163172.CrossRefGoogle ScholarPubMed
7. Settin, A, Abdel-Hady, H, El-Baz, R, Saber, I. Gene polymorphisms of TNF-α-308, IL-10-1082, IL-6-174 and IL-1RaVNTR related to susceptibility and severity of rheumatic heart disease. Pediatr Cardiol 2007; 28: 363371.CrossRefGoogle Scholar
8. Guilherme, L, Cury, P, Demarchi, LMF, et al. Rheumatic heart disease: proinflammatory cytokines play a role in the progression and maintenance of valvular lesions. Am J Pathol 2004; 165: 15831591.CrossRefGoogle ScholarPubMed
9. Bennermo, M, Held, C, Stemme, S, et al. Genetic predisposition of the interleukin-6 response to inflammation: implications for a variety of major diseases. Clin Chem 2004; 50: 21362140.CrossRefGoogle ScholarPubMed
10. Wu, SF, Chang, JS, Wan, L, Tsai, CH, Tsai, FJ. Association of IL-1Ra gene polymorphism, but no association of IL-1 ß and IL-4 gene polymorphisms with Kawasaki disease. J Clin Lab Anal 2005; 19: 99102.CrossRefGoogle Scholar
11. Rad, R, Dossumbekova, A, Neu, B, et al. Cytokine gene polymorphisms influence mucosal cytokine expression, gastric inflammation, and host specific colonisation during Helicobacter pylori infection. Gut 2004; 53: 10821089.CrossRefGoogle ScholarPubMed
12. Song, Z, Casolaro, V, Chen, R, Georas, SN, Monos, D, Ono, SJ. Polymorphic nucleotides within the human IL-4 promoter that mediate overexpression of the gene. J Immunol 1996; 156: 424429.CrossRefGoogle ScholarPubMed
13. Padyukov, L, Hytonen, AM, Smolnikova, M, et al. Polymorphism in promoter region of IL10 gene is associated with rheumatoid arthritis in women. J Rheumatol 2004; 31: 422425.Google ScholarPubMed
14. Rasouli, M, Kiany, S, Behbin, M. Interleukin-10 gene polymorphisms and susceptibility to brucellosis in Iranian patients. Iran J Immunol 2008; 5: 131135.Google ScholarPubMed
15. Sadiq, M, Islam, K, Abid, R, et al. Prevalence of rheumatic heart disease in school children of urban Lahore. Heart 2009; 95: 353357.CrossRefGoogle ScholarPubMed
16. Chou, HT, Tsai, CH, Chen, WC, Tsai, FJ. Lack of association of genetic polymorphisms in the interleukin-1beta, interleukin-1 receptor antagonist, interleukin-4, and interleukin-10 genes with risk of rheumatic heart disease in Taiwan Chinese. Int Heart J 2005; 46: 397406.CrossRefGoogle ScholarPubMed
17. Reuss, E, Fimmers, R, Kruger, A, Becker, C, Rittner, C, Hohler, T. Differential regulation of interleukin-10 production by genetic and environmental factors – a twin study. Genes Immun 2002; 3: 407413.CrossRefGoogle ScholarPubMed
18. Guilherme, L, Ramasawmy, R, Kalil, J. Rheumatic fever and rheumatic heart disease: genetics and pathogenesis. Scand J Immunol 2007; 66: 199207.CrossRefGoogle ScholarPubMed
19. Nakashima, H, Miyake, K, Inoue, Y, et al. Association between IL-4 genotype and IL-4 production in the Japanese population. Genes Immun 2002; 3: 107109.CrossRefGoogle ScholarPubMed
20. Turner, DM, Williams, DM, Sankaran, D, Lazarus, M, Sinnott, PJ, Hutchinson, IV. An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet 1997; 24: 18.CrossRefGoogle ScholarPubMed