The PTPN22 1858T allele but not variants in the proximal promoter region of IL-21 gene is associated with the susceptibility to type 1 diabetes and the presence of autoantibodies in a Brazilian cohort
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Citações na Scopus
11
Tipo de produção
article
Data de publicação
2013
Editora
WILEY-BLACKWELL
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Título da Revista
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Título do Volume
Autores
GAMBERINI, M.
RUIZ, M. O.
MATIOLI, S. R.
Autor de Grupo de pesquisa
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Citação
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, v.172, n.1, p.16-22, 2013
Resumo
Interleukin (IL)-21 and protein tyrosine phosphatase non-receptor 22 (PTPN22) regulate lymphocyte function and have been implicated in the pathogenesis of autoimmune diabetes. We sequenced the proximal promoter of the IL-21 gene for the first time and analysed the PTPN22 1858T polymorphism in type 1A diabetes (T1AD) patients and healthy controls (HC). We correlated the frequencies of islet and extra-pancreatic autoantibodies with genotypes from both loci. The case series comprised 612 T1AD patients and 792 HC. Genotyping of PTPN22 C1858T was performed on 434 T1AD patients and 689 HC. The 448 to +83 base pairs (bp) region of the IL-21 gene was sequenced in 309 Brazilian T1AD and 189 HC subjects. We also evaluated human leucocyte antigen (HLA) DR3/DR4 alleles. The frequencies of glutamic acid decarboxylase (GAD65), tyrosine phosphatase-like protein (IA)-2, anti-nuclear antibody (ANA), thyroid peroxidase (TPO), thyroglobulin (TG), thyrotrophin receptor autoantibody (TRAb), anti-smooth muscle (ASM) and 21-hydroxylase (21-OH) autoantibodies were higher in T1AD patients than in HC. The PTPN22 1858T allele was associated with an increased risk for developing T1AD [odds ratio (OR)=1 center dot 94; P<0 center dot 001], particularly in patients of European ancestry, and with a higher frequency of GAD65 and TG autoantibodies. HLA-DR3/DR4 alleles predominated in T1AD patients. A heterozygous allelic IL-21 gene variant (g.-241 T>A) was found in only one patient. In conclusion, only PTPN22 C1858T polymorphism and HLA-DR3 and/or DR4 alleles, but not allelic variants in the 5-proximal region of the IL-21 gene were associated with T1AD risk. Patients with T1AD had increased frequencies of anti-islet-cell, anti-thyroid, anti-nuclear, anti-smooth muscle and anti-21-OH autoantibodies. The C1858T PTPN22 polymorphism was also associated with a higher frequency of GAD65 and TG autoantibodies.
Palavras-chave
extra-pancreatic autoantibodies, islet-cell autoantibody, PTPN22C1858T gene variant, type 1 diabetes
Referências
- American Diabetes Association, 2011, DIABETES CARE S1, V34, pS62, DOI 10.2337/DC11-S062
- Arif S, 2011, DIABETES, V60, P2112, DOI 10.2337/db10-1643
- Asano K, 2007, HUM IMMUNOL, V68, P384, DOI 10.1016/j.humimm.2007.01.009
- Barrett JC, 2009, NAT GENET, V41, P703, DOI 10.1038/ng.381
- Bluestone JA, 2010, NATURE, V464, P1293, DOI 10.1038/nature08933
- Bottini N, 2004, NAT GENET, V36, P337, DOI 10.1038/ng1323
- Cattan D, 2011, WORLD J GASTROENTERO, V17, P543, DOI 10.3748/wjg.v17.i4.543
- Concannon P, 2009, NEW ENGL J MED, V360, P1646, DOI 10.1056/NEJMra0808284
- Criswell LA, 2005, AM J HUM GENET, V76, P561, DOI 10.1086/429096
- Datta S, 2008, PLOS ONE, V3, DOI 10.1371/journal.pone.0003118
- de Graaff LCG, 2011, NETH J MED, V69, P66
- Eisenbarth GS, 2009, TYPE 1 DIABETES CELL
- Ergür Ayça Törel, 2010, J Clin Res Pediatr Endocrinol, V2, P151, DOI 10.4274/jcrpe.v2i4.151
- Erichsen MM, 2009, J CLIN ENDOCR METAB, V94, P4882, DOI 10.1210/jc.2009-1368
- Ferraro A, 2011, DIABETES, V60, P2903, DOI 10.2337/db11-0090
- Grunnet LG, 2011, DIABETES, V60, P697, DOI 10.2337/db10-1782
- Hermann R, 2006, DIABETOLOGIA, V49, P1198, DOI 10.1007/s00125-006-0225-4
- Hiramatsu Y, 2010, J LEUKOCYTE BIOL, V87, P703, DOI 10.1189/jlb.0909639
- Ikegami H, 2007, DIABETES RES CLIN PR, V77, pS116, DOI 10.1016/j.diabres.2007.01.044
- Lahner E, 2009, WORLD J GASTROENTERO, V15, P5121, DOI 10.3748/wjg.15.5121
- Li YQ, 2005, J IMMUNOL, V175, P2261
- Lins TC, 2010, AM J HUM BIOL, V22, P187, DOI 10.1002/ajhb.20976
- Maiti AK, 2010, ARTHRITIS RHEUM-US, V62, P323, DOI 10.1002/art.27222
- Mehta DS, 2005, P NATL ACAD SCI USA, V102, P2016, DOI 10.1073/pnas.0409512102
- Mori M, 2005, J HUM GENET, V50, P264, DOI 10.1007/s10038-005-0246-8
- Monteleone Giovanni, 2009, Discov Med, V8, P113
- Parrish-Novak J, 2000, NATURE, V408, P57
- Peluso I, 2007, J IMMUNOL, V178, P732
- Petrelli A, 2011, DIABETES, V60, P3223, DOI 10.2337/db11-0880
- Rieck M, 2007, J IMMUNOL, V179, P4704
- Sarra M, 2010, CURR DRUG TARGETS, V11, P645
- Sivori S, 2003, EUR J IMMUNOL, V33, P3439, DOI 10.1002/eji.200324533
- Smyth D, 2004, DIABETES, V53, P3020, DOI 10.2337/diabetes.53.11.3020
- Staii Anca, 2010, Thyroid Res, V3, P11, DOI 10.1186/1756-6614-3-11
- Stanford SM, 2010, SEMIN IMMUNOPATHOL, V32, P127, DOI 10.1007/s00281-010-0201-4
- Sutherland APR, 2009, DIABETES, V58, P1144, DOI 10.2337/db08-0882
- Triolo TM, 2011, DIABETES CARE, V34, P1211, DOI 10.2337/dc10-1756
- Tsirogianni A, 2009, AUTOIMMUN REV, V8, P687, DOI 10.1016/j.autrev.2009.02.019
- Uibo R, 2011, CELL MOL IMMUNOL, V8, P150, DOI 10.1038/cmi.2010.66
- Zhang Li, 2008, Novartis Found Symp, V292, P85
- Zheng WP, 2005, DIABETES, V54, P906, DOI 10.2337/diabetes.54.3.906