The association of PTPN22 (rs2476601) and IL2RA (rs11594656) polymorphisms with T1D in Egyptian children

Abdelrahman, Hadeel M.; Sherief, Laila M.; Elrahman, Doaa M. Abd; Alghobashy, Ashgan Abdallah; Elsaadani, Hosam F.; Mohamed, Randa H.

doi:10.1016/j.humimm.2016.06.006

Cited by 13 publications

(14 citation statements)

References 33 publications

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“…Xia, Qin, and Zhao () found that the loci of IL2RA rs2104286 and rs12722489 are closely associated with increasing risk of multiple sclerosis in the Han and Hui nationalities. Abdelrahman et al () indicated that IL2RA was found to be associated with several autoimmune diseases including T1D, and IL2RA was more likely to develop T1D (OR = 2.8, p = 0.03) in Egyptian children. However, one study showed no significant relationship was observed between the polymorphism of IL2RA and T1D in children of northwest of Iran (Ranjouri et al, ).…”

Section: Dicussionmentioning

confidence: 99%

Genetic analysis of the relation between IL2RA/IL2RB and rheumatoid arthritis risk

Yang¹,

Yuan²,

Che³

et al. 2019

Molec Gen & Gen Med

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Background The biological mechanisms driving disease chronicity in rheumatoid arthritis (RA) are largely unidentified. Therefore, we aimed to determine genetic risk factors for RA. Methods In this case–control study, which includes samples from 499 patients and 507 healthy controls, six single‐nucleotide polymorphisms (SNPs) in interleukin‐2 receptor subunit alpha ( IL2RA ) and IL2RB were selected. Genotyping was performed using the Agena MassARRAY platform, and the statistical analyses were performed using the chi‐squared and Fisher's exact tests, genetic model analysis, and haplotype analysis. Result In the allele model, using the chi‐squared test, the result showed that rs791588 in IL2RA was associated with a decreased RA risk (odds ratios [OR] = 0.74, 95% confidence intervals [CI] = 0.62–0.89, p = 0.0014) after adjusting for age and gender. In the genetic model, logistic regression analyses revealed that rs791588 was associated with a decreased risk of RA under the codominant model, dominant model, recessive model, and log‐additive model. Stratification analysis revealed that two SNPs (rs791588 and rs2281089) were significantly associated with a reduced RA risk in an allele and genetic model after stratification by gender or age ( p < 0.05). In addition, the haplotypes “C rs12569923 G rs791588 ” and “C rs12569923 T rs791588 ” of IL2RA was associated with an increased risk of RA adjusted by age and gender (OR = 1.35, 95% CI: 1.12–1.64, p = 0.0016; OR = 1.24, 95% CI: 1.03–1.48, p = 0.021). Conclusion This finding indicates that the inherited altered genetic constitution at IL2RA may predispose to a less destructive course of RA.

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Section: Dicussionmentioning

confidence: 99%

Genetic analysis of the relation between IL2RA/IL2RB and rheumatoid arthritis risk

Yang¹,

Yuan²,

Che³

et al. 2019

Molec Gen & Gen Med

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“…In previous reports, our group observed that human leukocyte antigen (HLA)-DRB1*01 and HLA-A*28 alleles were associated with susceptibility to leprosy, whereas HLA-DRB1*08 was associated with resistance, in a Mexican mestizo population (23,24). The rs2476601 polymorphism of PTPN22 has been associated with a negative regulatory function in T-cell signaling and with autoimmune diseases including type 1 diabetes (25), rheumatoid arthritis (26) and systemic lupus erythematosus (27), and several infectious diseases including tuberculosis and leprosy (15)(16)(17)(18). Reduction of LYP activity by the 620W variant may affect the development of regulatory T lymphocytes (Tregs), thus affecting the balance between effector T cells and Tregs (28).…”

Section: Discussionmentioning

confidence: 94%

Analysis of the rs2476601 polymorphism of PTPN22 in Mexican mestizo patients with leprosy

et al. 2019

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Leprosy, a human chronic granulomatous disease caused by Mycobacterium leprae (M. leprae), remains endemic in certain countries despite the use of multidrug therapy. Recently, several host genes modulating the immune responses to M. leprae infection have been suggested to influence the acquisition and clinical course of leprosy. Lymphoid protein tyrosine phosphatase, encoded by the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene, serves a negative regulatory role in T cell activation. The non-synonymous single-nucleotide polymorphism (SNP) rs2476601 (1858C>T) has been associated with autoimmune diseases. Here, the present study investigated if rs2476601 polymorphism was associated with leprosy in a Mexican mestizo population. Genotyping was performed in patients with leprosy (n=189) and control subjects (n=231) from regions with higher incidence of leprosy. Genotypic (P=0.44) and allelic frequencies (P=0.45) of the rs2476601 polymorphism were similar between patients and controls; genotypic frequencies were 91 vs. 94% for CC and 9 vs. 6% for CT, and the TT genotype was absent in both groups. Allelic frequencies were 96 vs. 97% for C, and 4 vs. 3% for T. In the same way, the genotypic (P=0.46) and allelic frequencies (P=0.47) from MB patients and controls were similar. In conclusion, there was a lack of association of the PTPN22 rs2476601 polymorphism with the development of leprosy, which suggests that this SNP was not a genetic risk factor for leprosy in the Mexican mestizo population studied.

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“…A more recent report from China however, did find an association between the PTPN22 gene and T1DM [ 53 ]. In Egyptian T1DM patients, the TT genotype was detected in only 2% patients [ 54 ]. Similarly, in T1DM patients from North India, although the frequency of T allele of the PTPN22 gene was higher in T1DM patients (8%) compared to (2%) in the controls, none of the patients were homozygous for the TT genotype [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

Association of protein tyrosine phosphatase non-receptor type 22 gene functional variant C1858T, HLA-DQ/DR genotypes and autoantibodies with susceptibility to type-1 diabetes mellitus in Kuwaiti Arabs

et al. 2018

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The incidence of type-1 Diabetes Mellitus (T1DM) has increased steadily in Kuwait during recent years and it is now considered amongst the high-incidence countries. An interaction between susceptibility genes, immune system mediators and environmental factors predispose susceptible individuals to T1DM. We have determined the prevalence of protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene functional variant (C1858T; R620W, rs2476601), HLA-DQ and DR alleles and three autoantibodies in Kuwaiti children with T1DM to evaluate their impact on genetic predisposition of the disease. This study included 253 Kuwaiti children with T1DM and 214 ethnically matched controls. The genotypes of PTPN22 gene functional variant C1858T (R620W; rs2476601) were detected by PCR-RFLP method and confirmed by DNA sequencing. HLA-DQ and DR alleles were determined by sequence-specific PCR. Three autoantibodies were detected in the T1DM patients using radio-immunoassays. A significant association was detected between the variant genotype of the PTPN22 gene (C1858T, rs2476601) and T1DM in Kuwaiti Arabs. HLA-DQ2 and DQ8 alleles showed a strong association with T1DM. In T1DM patients which carried the variant TT-genotype of the PTPN22 gene, 93% had at least one DQ2 allele and 60% carried either a DQ2 or a DQ8 allele. Amongst the DR alleles, the DR3-DRB5, DR3-3, DR3-4 and DR4-4 showed a strong association with T1DM. Majority of T1DM patients who carried homozygous variant (TT) genotype of the PTPN22 gene had either DR3-DRB5 or DRB3-DRB4 genotypes. In T1DM patients who co-inherited the high risk HLA DQ, DR alleles with the variant genotype of PTPN22 gene, the majority were positive for three autoantibodies. Our data demonstrate that the variant T-allele of the PTPN22 gene along with HLA-DQ2 and DQ8 alleles constitute significant determinants of genetic predisposition of T1DM in Kuwaiti children.

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The association of PTPN22 (rs2476601) and IL2RA (rs11594656) polymorphisms with T1D in Egyptian children

Cited by 13 publications

References 33 publications

Genetic analysis of the relation between IL2RA/IL2RB and rheumatoid arthritis risk

Genetic analysis of the relation between IL2RA/IL2RB and rheumatoid arthritis risk

Analysis of the rs2476601 polymorphism of PTPN22 in Mexican mestizo patients with leprosy

Association of protein tyrosine phosphatase non-receptor type 22 gene functional variant C1858T, HLA-DQ/DR genotypes and autoantibodies with susceptibility to type-1 diabetes mellitus in Kuwaiti Arabs

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