Polymorphisms of the genes CTLA4, PTPN22, CD40, and PPARG and their roles in Graves' disease: susceptibility and clinical features.

Autor: Bufalo NE; Laboratory of Cancer Molecular Genetics, School of Medical Sciences (FCM), University of Campinas (UNICAMP), Campinas, São Paulo, Brazil. bufalo.ne@gmail.com., Dos Santos RB; Division of Endocrinology, Pontifical Catholic University of Campinas (PUCCAMP), Campinas, São Paulo, Brazil., Rocha AG; Laboratory of Cancer Molecular Genetics, School of Medical Sciences (FCM), University of Campinas (UNICAMP), Campinas, São Paulo, Brazil., Teodoro L; Laboratory of Cancer Molecular Genetics, School of Medical Sciences (FCM), University of Campinas (UNICAMP), Campinas, São Paulo, Brazil., Romaldini JH; Division of Endocrinology, Pontifical Catholic University of Campinas (PUCCAMP), Campinas, São Paulo, Brazil.; Endocrinology Service, São Paulo State Public Servant's Hospital, Institute of Medical Assistance of the State Public Servant (HSPE-IAMSPE), São Paulo, SP, Brazil., Ward LS; Laboratory of Cancer Molecular Genetics, School of Medical Sciences (FCM), University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
Jazyk: angličtina
Zdroj: Endocrine [Endocrine] 2021 Jan; Vol. 71 (1), pp. 104-112. Date of Electronic Publication: 2020 May 17.
DOI: 10.1007/s12020-020-02337-x
Abstrakt: Purpose: CTLA4, PTPN22, and CD40 are immune-regulatory genes strongly associated with GD, as well as PPARG, but their clinical significance in different populations is still uncertain.
Methods: We genotyped 282 Brazilian GD patients (234 women and 48 men, 39.80 ± 11.69 years old), including 144 patients with GO, and 308 healthy control individuals (246 women and 62 men, 36.86 ± 12.95 years old).
Results: A multivariate analysis demonstrated that the inheritance of the GG genotype rs3087243 of CTLA4 (OR = 2.593; 95% CI = 1.630-4.123; p < 0.0001) and the CC genotype of rs3789607 of PTPN22 (OR = 2.668; 95% CI = 1.399-5.086; p = 0.0029) consisted in factors independent of the susceptibility to GD. The inheritance of polymorphic genotypes of rs5742909 of CTLA4 was associated with older age at the time of diagnosis (42.90 ± 10.83 versus 38.84 ± 11.81 years old; p = 0.0105), with higher TRAb levels (148.17 ± 188.90 U/L versus 112.14 ± 208.54 U/L; p = 0.0229) and the need for higher therapeutic doses of radioiodine (64.23 ± 17.16 versus 50.22 ± 16.86; p = 0.0237). The inheritance of the CC genotype of rs1883832 CD40 gene was more frequent among women (69.65%) than men (52.00%; p = 0.0186). The polymorphic genotype of PPARG gene (rs1801282) was associated with TPOAb positivity (p = 0.0391), and the GG genotype of rs2476601 of PTPN22 gene was associated with positivity for both TgAb (p = 0.0360) and TPOAb (p < 0.0001). Both polymorphic genotypes rs2476601 and rs3789607 of the PTPN22 gene were more frequent among nonsmoking patients (p = 0.0102 and p = 0.0124, respectively).
Conclusions: Our data confirm the important role of CTLA4 polymorphisms in GD susceptibility; demonstrate the role of PTPN22 polymorphisms in patients' clinical features; and suggest these genes may influence the severity of the disease.
Databáze: MEDLINE
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