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

  • Authors:
    • Mónica Escamilla‑Tilch
    • Thalía Gabriela Pérez‑Suárez
    • Nora Magdalena Torres‑Carrillo
    • Rosario Rodríguez‑Guillén
    • Roberto Arenas‑Guzmán
    • Marcela Torres‑Hernández
    • Mary Fafutis‑Morris
    • Sergio Estrada‑Parra
    • Iris Estrada‑García
    • Maricela García‑Lechuga
    • Julio Granados
    • Rosalio Ramos‑Payan
  • View Affiliations

  • Published online on: January 7, 2019     https://doi.org/10.3892/br.2019.1184
  • Pages: 127-132
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Abstract

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.

Introduction

Leprosy remains an important health issue worldwide, particularly in Asia, Africa and Latin America (1). The disease is caused by Mycobacterium leprae, an obligate intracellular acid-fast bacillus that causes a chronic granulomatous infection of the skin and peripheral nerves of susceptible individuals, triggering irreversible impairment of nerve function and consequent chronic disability (2). Based on clinical, histological, bacteriological and immunological characteristics, the Ridley-Jopling (3) classification defines leprosy as: i) Lepromatous leprosy (LL); ii) tuberculoid leprosy (TT), and three dimorphic (D) forms; iii) borderline tuberculoid (BT), iv) borderline borderline (BB); and v) borderline lepromatous (BL). In addition, the World Health Organization (WHO) defines BB, BL and LL patients as multibacillary (MB) and BT and TT patients as paucibacillary (3,4).

Genetic factors, particularly host genes that modulate immune responses, have been suggested to favor the acquisition of leprosy and the clinical course of the disease (5,6). Lymphoid protein tyrosine phosphatase (LYP) is an enzyme encoded by the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene located at chromosome 1p13.3-13.1. This protein belongs to the PEST group of nonreceptor classical class I PTPs (protein tyrosine phosphatase), characterized to be cysteine-based and restricted to hematopoietic cells, mainly lymphoid cells (7-9). Therefore, LYP is expressed in developing T cells and negatively regulates T-cell signaling by acting together with the tyrosine-protein kinase Csk, a potent suppressor of T-cell activation, to inhibit this activation through the T-cell receptor (TCR) (10,11). The transitional mutation rs2476601 in exon 14 of the PTPN22 gene changes a cytosine to a thymine at position 1858 (1858C>T), resulting in a single amino acid change of an arginine to a tryptophan at codon 620 (R620W) (12). Consequently, the mutated 1858T allele encodes LYP-Trp620, a more efficient inhibitor of T cell activation than the normal LYP-Arg620. LYP-Trp620 is a gain-of-function variant involved in the earliest events of TCR signaling; for example, it decreases the leukocyte-specific protein tyrosine kinase-mediated phosphorylation of the TCRs chain (13).

Bottini et al (12) were the first to report an association between polymorphism rs2476601 of PTPN22 and type 1 diabetes mellitus in North American and Italian populations. Further studies have indicated that rs2476601 participates in the susceptibility to gram-positive infections (14), protection from tuberculosis (15,16) and susceptibility to leprosy (17,18).

Therefore, the aim of the present study was to analyze the association between polymorphism rs2476601 of PTPN22 gene with the susceptibility to developing leprosy in Mexican patients, using TaqMan Pre-Designed single nucleotide polymorphism (SNP) genotyping assays.

Materials and methods

Subjects

A total of 189 leprosy patients from the Mexican states with higher incidence of leprosy: Sinaloa, Guadalajara, Michoacán, Oaxaca, Guanajuato, Mexico City and Guerrero, were recruited from July 2011 to January 2016 and classified according to Ridley-Jopling and WHO criteria (3,4). Of these, 165 cases were MB (141 LL and 24 D) and 24 cases were PB. Patients were 44% female and 56% male with a mean age of 52±18.8 years old. A control group comprised of 231 healthy unrelated subjects matched by ethnicity (42% female and 58% male, with a mean age of 78±12 years). All study participants were classified as Mexican mestizos (19,20). The investigation was performed according to the ethical guidelines of the 2008 Declaration of Helsinki. The Ethics and Research Committee of the Faculty of Biological and Chemical Sciences, Autonomous University of Sinaloa (Culiacán, Mexico), approved the study. Written informed consent was provided by all study participants prior to enrollment.

Genotyping

Total genomic DNA, from patients and healthy subjects, was extracted from samples of peripheral blood (5 ml) following Miller's salting-out method (21). Genotyping for rs2476601 (1858C>T, R620W) in the PTPN22 gene was performed using a Real Time Thermocycler (StepOnePlus; Applied Biosystems; Thermo Fisher Scientific, Inc., Waltham, MA, USA) and TaqMan Pre-Designed SNP genotyping assays method. C_16021387_20 was the SNP genotyping assay ID (Applied Biosystems; Thermo Fisher Scientific, Inc.). Genotyping assays were performed according to manufacturer's protocols. Optimization of the TaqMan SNP genotyping assay was performed using controls of known CC, CT and TT genotypes selected through DNA sequencing.

Statistical analysis

Demographic and clinical variables of leprosy patients and controls were presented as mean ± standard deviation and frequencies. Hardy-Weinberg equilibrium and genotypic and allelic frequencies were assessed using the χ2 test. SNP associations were measured by odds ratio (OR) with 95% confidence interval (CI). P<0.05 was considered to indicate a statistically significant difference. PASW v18.0 (SPSS, Inc., Chicago, IL, USA) software was used for analysis.

Results

Population characteristics

We investigated the possible association between polymorphism rs2476601 of PTPN22 and leprosy in 420 Mexican mestizo individuals (189 patients with leprosy and 231 healthy controls). The demographic and clinical data of the patients with leprosy are presented in Table I.

Table I.

Demographic characteristics and patterns of 1858C>T polymorphism in PTPN22 among leprosy patients.

Table I.

Demographic characteristics and patterns of 1858C>T polymorphism in PTPN22 among leprosy patients.

 Geographic distribution of leprosy patients (n=189)
DemographicSinaloa (n=101)Guadalajara (n=38)Michoacán (n=24)Oaxaca (n=13)Guanajuato (n=6)Nayarit (n=3)Mexico City (n=3)Guerrero (n=1)
Sex, M/F53/4827/1111/139/44/22/12/11/0
Age in years, M/F45±16.4/37±13.755±17.7/59±9.377±7.6/61±21.136±12.6/42±15.275±10.5/86±12.737±16.2/66±11.352±2.8/51±18.527±6.0/0.0
Classification, n
     I90040000
     TT13510000
     D165020111
     LL75301966221
Genotypic frequencies, %
     TT00000000
     CT611120033330
     CC9489881001006767100
Allelic frequencies, %
     T3560017170
     C9795941001008383100

[i] PTPN22, protein tyrosine phosphatase non-receptor type 22; I, indeterminate leprosy; TT, tuberculoid leprosy; D, dimorphic forms of leprosy; LL, lepromatous leprosy; M, male; F, female.

Genotypic and allelic frequencies of polymorphism rs2476601 of PTPN22

The SNP rs2476601 was in Hardy-Weinberg equilibrium in patients and controls (data not shown; P>0.05). The distributions of allelic and genotypic frequencies between both groups are displayed in Table II. Genotypic frequencies did not differ significantly (P=0.44) between patients and controls: the frequencies were 91 vs. 94% for CC; 9 vs. 6% for CT; and the TT genotype was absent in both groups. Allelic frequencies in patients and controls were: 96 vs. 97% for C; and 4 vs. 3% for T (P=0.45).

Table II.

Allelic and gene frequencies of 1858C>T polymorphism in PTPN22 in patients with leprosy and healthy controls.

Table II.

Allelic and gene frequencies of 1858C>T polymorphism in PTPN22 in patients with leprosy and healthy controls.

1858C>TLeprosy, n (%)Controls, n (%)P-valueOR (95% CI)
Genotypen=189n=231  
     CC173(91)217(94)--
     CT16(9)14(6)0.440.69 (0.33-1.46)
     TT0 (0)0 (0)--
Allelen=378n=462  
     C362(96)448(97)--
     T16(4)14(3)0.450.70 (0.34-1.46)

[i] The values are presented as frequency in percentage and number of the genotype or allele. The frequencies were compared between the groups by the χ2 test. Statistical significance was determined at P<0.05. PTPN22, protein tyrosine phosphatase non-receptor type 22; OR, odds ratio; CI, confidence interval.

Additionally, the association with MB cases was examined as it is the most frequent clinical phenotype of leprosy in the Mexican population (22). Table III shows the genotypic and allelic frequencies (P=0.46 and P=0.47, respectively) between MB patients and controls. The frequencies were the same as those observed in leprosy generally (Table II).

Table III.

Allelic and gene frequencies of 1858 C>T polymorphism in PTPN22 in patients with MB leprosy and healthy controls.

Table III.

Allelic and gene frequencies of 1858 C>T polymorphism in PTPN22 in patients with MB leprosy and healthy controls.

1858C>TMB patients, n (%)Controls, n (%)P-valueOR (95% CI)
Genotypen=165n=231  
     CC151(91)217(94)--
     CT14(9)14(6)0.460.69 (0.32-1.50)
     TT0 (0)0 (0)--
Allelen=330n=462  
     C316(96)448(97)--
     T14(4)14(3)0.470.70 (0.33-1.50)

[i] The values are presented as frequency in percentage and number of the genotype or allele. The frequencies were compared between the groups was analyzed by the χ2 test. Statistical significance was determined at P<0.05. PTPN22, protein tyrosine phosphatase non-receptor type 22; OR, odds ratio; CI, confidence interval; MB multibacillary leprosy.

Table IV presents the frequencies that correspond to the clinical subtypes of MB. Genotypic frequencies between the D forms of MB leprosy (BB and BL) and controls were 92 vs. 94% for CC, and 8 vs. 6% for CT (P=0.90); between LL patients and controls were 91 vs. 94% for CC, and 9 vs. 6% for CT (P=0.49); and between LL and D patients were 91 vs. 92% for CC, and 9 vs. 8% for CT (P=1.00). As shown, TT genotype was absent in patients and controls. Allelic frequencies between D patients and controls were 94 vs. 98% for the C allele, and 6 vs. 2% for the T allele (P=0.49); between LL patients and controls were 96 vs. 98% for the C allele, and 4 vs. 2% for the T allele (P=0.68); and between LL and D patients were 96 vs. 94% for the C allele, and 4 vs. 6% for the T allele (P=0.76). Thus, overall, no association was observed between patients with MB leprosy and the polymorphism rs2476601 of PTPN22.

Table IV.

Allelic and gene frequencies of 1858 C>T polymorphism into PTPN22 in subclinical forms (LL and D) and healthy controls.

Table IV.

Allelic and gene frequencies of 1858 C>T polymorphism into PTPN22 in subclinical forms (LL and D) and healthy controls.

1858 C>TD patients, n (%)Controls, n (%) P-valueaOR (95% CI)LL patients, n (%) P-valuebOR (95% CI) P-valuecOR (95% CI)
Genotypen=24n=231  n=141    
     CC22(92)217(94)--129(91)----
     CT2(8)14(6)0.900.70 (0.15-3.32)12(9)0.490.69 (0.31-1.54)1.00.97 (0.20-4.66)
     TT0 (0)0 (0)--0 (0)----
Allelen=48n=462  n=282    
     C51(94)482(98)--295(96)----
     T3(6)14(2)0.490.49 (0.13-1.77)11(4)0.680.77 (0.34-1.73)0.761.57 (0.42-5.85)

[i] The values are presented as frequency in percentage and number of the genotype or allele. The frequencies were compared between groups by the χ2 test. Statistical significance was at P<0.05. aD patients vs. controls;

[ii] bLL patients vs. controls;

[iii] cD vs. LL patients. PTPN22, protein tyrosine phosphatase non-receptor type 22; OR, odds ratio; CI, confidence interval; D, dimorphic forms of leprosy; LL, lepromatous leprosy.

Discussion

Although leprosy is of infectious etiology, studies have demonstrated that a genetic component and its variability serve a crucial role in the establishment and progression of the disease (5,6). 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 (15-18). 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). Accordingly, T cells appear anergic to M. leprae antigens in leprosy patients (18). Patients with LL have been found to exhibit an increase of CD25hi cells as compared to tuberculoid and healthy subjects, however there were also low levels of interferon (INF)-γ and interleukin (IL)-17 in patients with CD25hi cells, therefore the Tregs may have contributed to the decrease via regulation of lymphocytes T (29). By contrast, an increase in forkhead box P3 in circulating LL patients has been observed due to an increase of transforming growth factor-β produced by T helper 3 cells (30). In this context, the current study analyzed the association between rs2476601 polymorphism of PTPN22 with leprosy in a Mexican mestizo population. The distribution of the patients was in accordance with that reported by Larrea et al (22); among the states with the highest prevalence of leprosy were Sinaloa, Guadalajara and Michoacán, and there was a higher prevalence in men than in women, with an increased proportion of MB cases.

In agreement with one of seemingly only two other works studying this polymorphism in leprosy (17,18), the current results indicates no association between genotypic and allelic frequencies of rs2476601 and susceptibility of developing leprosy. Rani et al (18) observed a significant difference in the frequency of the 1858T allele between patients with lepromatous or tuberculoid leprosy and healthy controls in an Indian population, suggesting that this translocation contributes to T-cell signaling malfunction. By contrast, Aliparasti et al (17) observed no difference in the distribution of genotypic and allelic frequencies of this polymorphism between leprosy patients and healthy controls in an Iranian population. The presence or absence of the 1858T allele may be associated with ethnicity, as previous studies have observed high frequency of this allele in Europeans (14) and low frequency in Asians (31). In agreement, Mexican mestizo patients exhibit a low frequency of the TT genotype of this allele (32). In general, these conflicting results suggest the existence of more than one mechanism leading to the observed T cell anergy in leprosy, independent or complementary to TCR regulation by LYP. In this sense, Sridevi et al (33) proposed a defective macrophage-T cell interaction as a mechanism leading to the low levels of the co-stimulatory molecules CD28, CD80 and CD86, as well as the low production of IL-2 and INF-γ, observed in LL patients. More studies are required to further evaluate the association of polymorphisms of genes participating in immune-synapse interactions as potential risk factors for leprosy.

In conclusion, in the present study, the rs2476601 polymorphism of PTPN22 did not appear be a genetic risk factor for leprosy in a Mexican mestizo population, perhaps due to the low frequency of the T allele and the absence of carriers of the TT genotype in both patients and controls. The present report is one of few studies that have evaluated the role of rs2476601 in the development and clinical course of leprosy, and further study is required in populations with different ethnic background.

Acknowledgements

The authors are thankful to Dr Guzman Sanchez-Schmitz. (Boston Children's Hospital and Harvard Medical School, Boston, ΜΑ, USA) for critically reading and revising the manuscript on language, and Jesús Lázaro López-Vázquez (Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico) for their role as a laboratory assistant.

Funding

This study was supported by the National Council of Science and Technology (CONACYT, grant no. 106152).

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author.

Authors' contributions

RAG, MFM and MGL diagnosed and treated the patients. MET, TGPS and NMTC conducted laboratory test. RRG, MTH and SEP collected the data and analyzed the results. RRP, IEG and JG wrote the manuscript. All authors read and approved the final manuscript.

Ethics approval and consent to participate

The Ethics and Research Committee of the Faculty of Biological and Chemical Sciences, Autonomous University of Sinaloa, approved the study. Written informed consent was provided by all study participants prior to enrollment.

Patient consent for publication

Not applicable.

Competing interests

The authors declare no competing interests related to this manuscript.

References

1 

World Health Organization (WHO): Leprosy. WHO, Geneva. 2018.https://www.who.int/en/news-room/fact-sheets/detail/leprosy. Accessed February 9, 2018.

2 

Britton WJ and Lockwood DN: Leprosy. Lancet. 363:1209–1219. 2004.PubMed/NCBI View Article : Google Scholar

3 

Ridley DS and Jopling WH: Classification of leprosy according to immunity. A five-group system. Int J Lepr Other Mycobact Dis. 34:255–273. 1966.PubMed/NCBI

4 

Mira MT: Genetic host resistance and susceptibility to leprosy. Microbes Infect. 8:1124–1131. 2006.PubMed/NCBI View Article : Google Scholar

5 

Alter A, Grant A, Abel L, Alcais A and Schurr E: Leprosy as a genetic disease. Mamm Genome. 22:19–31. 2011.PubMed/NCBI View Article : Google Scholar

6 

Zhang FR, Huang W, Chen SM, Sun LD, Liu H, Li Y, Cui Y, Yan XX, Yang HT, Yang RD, et al: Genomewide association study of leprosy. N Engl J Med. 361:2609–2618. 2009.PubMed/NCBI View Article : Google Scholar

7 

Alonso A, Sasin J, Bottini N, Friedberg I, Friedberg I, Osterman A, Godzik A, Hunter T, Dixon J and Mustelin T: Protein tyrosine phosphatases in the human genome. Cell. 117:699–711. 2004.PubMed/NCBI View Article : Google Scholar

8 

Andersen JN, Jansen PG, Echwald SM, Mortensen OH, Fukada T, Del Vecchio R, Tonks NK and Møller NP: A genomic perspective on protein tyrosine phosphatases: Gene structure, pseudogenes, and genetic disease linkage. FASEB J. 18:8–30. 2004.PubMed/NCBI View Article : Google Scholar

9 

Davidson D, Cloutier JF, Gregorieff A and Veillette A: Inhibitory tyrosine protein kinase p50csk is associated with protein-tyrosine phosphatase PTP-PEST in hemopoietic and non-hemopoietic cells. J Biol Chem. 272:23455–23462. 1997.PubMed/NCBI View Article : Google Scholar

10 

Cloutier JF and Veillette A: Cooperative inhibition of T-cell antigen receptor signaling by a complex between a kinase and a phosphatase. J Exp Med. 189:111–121. 1999.PubMed/NCBI View Article : Google Scholar

11 

Davidson D and Veillette A: PTP-PEST, a scaffold protein tyrosine phosphatase, negatively regulates lymphocyte activation by targeting a unique set of substrates. EMBO J. 20:3414–3426. 2001.PubMed/NCBI View Article : Google Scholar

12 

Bottini N, Musumeci L, Alonso A, Rahmouni S, Nika K, Rostamkhani M, MacMurray J, Meloni GF, Lucarelli P, Pellecchia M, et al: A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes. Nat Genet. 36:337–338. 2004.PubMed/NCBI View Article : Google Scholar

13 

Vang T, Congia M, Macis MD, Musumeci L, Orrú V, Zavattari P, Nika K, Tautz L, Taskén K, Cucca F, et al: Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant. Nat Genet. 37:1317–1319. 2005.PubMed/NCBI View Article : Google Scholar

14 

Chapman SJ, Khor CC, Vannberg FO, Maskell NA, Davies CW, Hedley EL, Segal S, Moore CE, Knox K, Day NP, et al: PTPN22 and invasive bacterial disease. Nat Genet. 38:499–500. 2006.PubMed/NCBI View Article : Google Scholar

15 

Lamsyah H, Rueda B, Baassi L, Elaouad R, Bottini N, Sadki K and Martin J: Association of PTPN22 gene functional variants with development of pulmonary tuberculosis in Moroccan population. Tissue Antigens. 74:228–232. 2009.PubMed/NCBI View Article : Google Scholar

16 

Lopez-Escamez JA: A variant of PTPN22 gene conferring risk to autoimmune diseases may protect against tuberculosis. J Postgrad Med. 56:242–243. 2010.PubMed/NCBI

17 

Aliparasti MR, Almasi S, Majidi J, Zamani F, Khoramifar AR and Azari ARF: Protein tyrosine phosphatase non-receptor type 22 gene polymorphism C1858T is not associated with leprosy in Azerbaijan, Northwest Iran. Indian J Hum Genet. 19:403–407. 2013.PubMed/NCBI View Article : Google Scholar

18 

Rani R, Singh A, Israni N, Singh A, Sharma P and Kar HK: The role of polymorphic protein tyrosine phosphatase non-receptor type 22 in leprosy. J Invest Dermatol. 129:2726–2728. 2009.PubMed/NCBI View Article : Google Scholar

19 

Rangel-Villalobos H, Muñoz-Valle JF, González-Martín A, Gorostiza A, Magaña MT and Páez-Riberos LA: Genetic admixture, relatedness, and structure patterns among Mexican populations revealed by the Y-chromosome. Am J Phys Anthropol. 135:448–461. 2008.PubMed/NCBI View Article : Google Scholar

20 

Rubi-Castellanos R, Anaya-Palafox M, Mena-Rojas E, Bautista-España D, Muñoz-Valle JF and Rangel-Villalobos H: Genetic data of 15 autosomal STRs (Identifiler kit) of three Mexican Mestizo population samples from the States of Jalisco (West), Puebla (Center), and Yucatan (Southeast). Forensic Sci Int Genet. 3:e71–e76. 2009.PubMed/NCBI View Article : Google Scholar

21 

Miller SA, Dykes DD and Polesky HF: A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 16(1215)1988.PubMed/NCBI

22 

Larrea MR, Carreño MC and Fine PE: Patterns and trends of leprosy in Mexico: 1989-2009. Lepr Rev. 83:184–194. 2012.PubMed/NCBI

23 

Aguilar-Medina M, Escamilla-Tilch M, Frías-Castro LO, Romero-Quintana G, Estrada-García I, Estrada-Parra S, Granados J, Arambula Meraz E, Sánchez-Schmitz G, Khader SA, et al: HLA Alleles are genetic markers for susceptibility and resistance towards leprosy in a Mexican Mestizo population. Ann Hum Genet. 81:35–40. 2017.PubMed/NCBI View Article : Google Scholar

24 

Escamilla-Tilch M, Torres-Carrillo NM, Payan RR, Aguilar-Medina M, Salazar MI, Fafutis-Morris M, Arenas-Guzman R, Estrada-Parra S, Estrada-Garcia I and Granados J: Association of genetic polymorphism of HLA-DRB1 antigens with the susceptibility to lepromatous leprosy. Biomed Rep. 1:945–949. 2013.PubMed/NCBI View Article : Google Scholar

25 

Abdelrahman HM, Sherief LM, Abd Elrahman DM, Alghobashy A, Elsaadani HF and Mohamed RH: The association of PTPN22 (rs2476601) and IL2RA (rs11594656) polymorphisms with T1D in Egyptian children. Hum Immunol. 77:682–686. 2016.PubMed/NCBI View Article : Google Scholar

26 

Song GG, Bae SC, Kim JH and Lee YH: The PTPN22 C1858T polymorphism and rheumatoid arthritis: A meta-analysis. Rheumatol Int. 33:1991–1999. 2013.PubMed/NCBI View Article : Google Scholar

27 

Zheng J, Ibrahim S, Petersen F and Yu X: Meta-analysis reveals an association of PTPN22 C1858T with autoimmune diseases, which depends on the localization of the affected tissue. Genes Immun. 13:641–652. 2012.PubMed/NCBI View Article : Google Scholar

28 

Maine CJ, Hamilton-Williams EE, Cheung J, Stanford SM, Bottini N, Wicker LS and Sherman LA: PTPN22 alters the development of regulatory T cells in the thymus. J Immunol. 188:5267–5275. 2012.PubMed/NCBI View Article : Google Scholar

29 

Saini C, Ramesh V and Nath I: Increase in TGF-β secreting CD4(+)CD25(+) FOXP3(+) T regulatory cells in anergic lepromatous leprosy patients. PLoS Negl Trop Dis. 8(e2639)2014.PubMed/NCBI View Article : Google Scholar

30 

Kumar S, Naqvi RA, Ali R, Rani R, Khanna N and Rao DN: FoxP3 provides competitive fitness to CD4(+)CD25(+) T cells in leprosy patients via transcriptional regulation. Eur J Immunol. 44:431–439. 2014.PubMed/NCBI View Article : Google Scholar

31 

Kawasaki E, Awata T, Ikegami H, Kobayashi T, Maruyama T, Nakanishi K, Shimada A, Uga M, Kurihara S, Kawabata Y, et al: Systematic search for single nucleotide polymorphisms in a lymphoid tyrosine phosphatase gene (PTPN22): association between a promoter polymorphism and type 1 diabetes in Asian populations. Am J Med Genet A. 140:586–593. 2006.PubMed/NCBI View Article : Google Scholar

32 

Torres-Carrillo NM, Ruiz-Noa Y, Martínez-Bonilla GE, Leyva-Torres SD, Torres-Carrillo N, Palafox-Sánchez CA, Navarro-Hernández RE, Rangel-Villalobos H, Oregón-Romero E and Muñoz-Valle JF: The +1858C/T PTPN22 gene polymorphism confers genetic susceptibility to rheumatoid arthritis in Mexican population from the Western Mexico. Immunol Lett. 147:41–46. 2012.PubMed/NCBI View Article : Google Scholar

33 

Sridevi K, Neena K, Chitralekha KT, Arif AK, Tomar D and Rao DN: Expression of costimulatory molecules (CD80, CD86, CD28, CD152), accessory molecules (TCR alphabeta, TCR gammadelta) and T cell lineage molecules (CD4+, CD8+) in PBMC of leprosy patients using Mycobacterium leprae antigen (MLCWA) with murabutide and T cell peptide of Trat protein. Int Immunopharmacol. 4:1–14. 2004.PubMed/NCBI View Article : Google Scholar

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Escamilla‑Tilch M, Pérez‑Suárez TG, Torres‑Carrillo NM, Rodríguez‑Guillén R, Arenas‑Guzmán R, Torres‑Hernández M, Fafutis‑Morris M, Estrada‑Parra S, Estrada‑García I, García‑Lechuga M, García‑Lechuga M, et al: Analysis of the rs2476601 polymorphism of PTPN22 in Mexican mestizo patients with leprosy. Biomed Rep 10: 127-132, 2019.
APA
Escamilla‑Tilch, M., Pérez‑Suárez, T.G., Torres‑Carrillo, N.M., Rodríguez‑Guillén, R., Arenas‑Guzmán, R., Torres‑Hernández, M. ... Ramos‑Payan, R. (2019). Analysis of the rs2476601 polymorphism of PTPN22 in Mexican mestizo patients with leprosy. Biomedical Reports, 10, 127-132. https://doi.org/10.3892/br.2019.1184
MLA
Escamilla‑Tilch, M., Pérez‑Suárez, T. G., Torres‑Carrillo, N. M., Rodríguez‑Guillén, R., Arenas‑Guzmán, R., Torres‑Hernández, M., Fafutis‑Morris, M., Estrada‑Parra, S., Estrada‑García, I., García‑Lechuga, M., Granados, J., Ramos‑Payan, R."Analysis of the rs2476601 polymorphism of PTPN22 in Mexican mestizo patients with leprosy". Biomedical Reports 10.2 (2019): 127-132.
Chicago
Escamilla‑Tilch, M., Pérez‑Suárez, T. G., Torres‑Carrillo, N. M., Rodríguez‑Guillén, R., Arenas‑Guzmán, R., Torres‑Hernández, M., Fafutis‑Morris, M., Estrada‑Parra, S., Estrada‑García, I., García‑Lechuga, M., Granados, J., Ramos‑Payan, R."Analysis of the rs2476601 polymorphism of PTPN22 in Mexican mestizo patients with leprosy". Biomedical Reports 10, no. 2 (2019): 127-132. https://doi.org/10.3892/br.2019.1184