PD1.5 variant on PDCD1 gene, regulator of T lymphocyte activity, influences non-muscle-invasive bladder cancer risk.

BACKGROUND: Since failure in recognition of abnormal cells by the immune system has an important role in bladder cancer development and progression, this study aimed to evaluate whether PD1 (c.627+252C>T) and PD1.5 (c.804C>T) single-nucleotide variants (SNVs) in PDCD1 gene, enrolled in modulation of T lymphocyte activity, influence risk, clinicopathological aspects, and outcome of non-muscle-invasive bladder cancer (NMIBC) patients. MATERIAL AND METHODS: DNA genotyping by real-time polymerase chain reaction was offered to 160 non muscle invasive bladder cancer (NMIBC) patients and 250 controls. One hundred and twenty-seven patients treated with bladder transurethral resection and intravesical bacillus Calmette-Guérin were enrolled in survival analyses. RESULTS: Individuals with PD1.5 CC genotype had 2.3-fold increased risk of developing NMIBC. Similar genotype and haplotype frequencies were seen in patients stratified by clinicopathological aspects. Patients with T allele, CT or TT plus CT or TT genotype and TT haplotype of PD1 and PD1.5 SNVs had up to 4.0-times greater chances of presenting NMIBC relapse and death by any cause than the remaining patients, but analysis of NMIBC specific survival was not possible in study due to the small number of patients evolving to death during follow up. CONCLUSIONS: Our data presented for the first time, preliminary evidence that inherited abnormality in regulation of T lymphocyte activity alters NMIBC risk.

PDCD1 gene polymorphisms as regulators of T-lymphocyte activity in cutaneous melanoma risk and prognosis.

This study aimed to evaluate whether PD1.1 (c.-606G>A), PD1 (c.627 + 252C>T), PD1.5 (c.804C>T), and PD1.9 (c.644C>T) single nucleotide polymorphisms of PDCD1 gene influence the risk, clinicopathological aspects, and survival of cutaneous melanoma (CM). Individuals with phototype I or II and PD1 CC genotype were under 5.89-fold increased risk of developing CM. PD1.5 TT genotype increased PDCD1 expression (2.49 versus 1.28 arbitrary units, p = .03) and PD1.5 CT or TT genotype and allele T increased PD1 expression in TCD4+ lymphocytes (16.6 versus 12.5%, p = .01; 17.0 versus 13.1%, p = .006). At 60 months of follow-up, short recurrence-free survival was seen in patients with PD1.1 AA genotype (33.3 versus 71.8%, p = .03). Patients with PD1.1 AA and PD1.5 CC genotype had 4.21 and 2.62 more chances of presenting relapse and evolving death by disease in Cox analyses, respectively. Our data provide preliminary evidence that abnormalities in regulation of T lymphocyte alter CM risk, clinical aspects, and prognosis.

Association of PDCD1 polymorphism to systemic lupus erythematosus and rheumatoid arthritis susceptibility.

OBJECTIVE: This study aims to analyze the relationship of programmed cell death 1 (PDCD1) gene polymorphism (PD1.3G/A - rs11568821) with features of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in a Southern Brazilian population. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed in 95 SLE and 87 RA patients and 128 control group individuals from Santa Catarina, Southern Brazil. The Hardy-Weinberg equilibrium (HWE) test, and odds ratio (OR) were analyzed, considering CI 95% and p≤0.05. RESULTS: The PD1.3A allele frequencies were 0.095 (SLE), 0.115 (RA) and 0.078 (controls). The genotypes of the control group were in HWE, while those of SLE and RA patients were not. However, we found no association between PD1.3 polymorphism and the SLE or RA susceptibility, nor clinical or epidemiological data. CONCLUSION: There was no significant association between PD1.3 polymorphism and SLE or RA susceptibility in this Southern Brazilian population.

Association of PDCD1 polymorphism to systemic lupus erythematosus and rheumatoid arthritis susceptibility / Associação entre o polimorfismo do gene PDCD1 e a susceptibilidade ao lúpus eritematoso sistêmico e à artrite reumatoide

ABSTRACT Objective: This study aims to analyze the relationship of programmed cell death 1 (PDCD1) gene polymorphism (PD1.3G/A - rs11568821) with features of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in a Southern Brazilian population. Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed in 95 SLE and 87 RA patients and 128 control group individuals from Santa Catarina, Southern Brazil. The Hardy-Weinberg equilibrium (HWE) test, and odds ratio (OR) were analyzed, considering CI 95% and p ≤ 0.05. Results: The PD1.3A allele frequencies were 0.095 (SLE), 0.115 (RA) and 0.078 (controls). The genotypes of the control group were in HWE, while those of SLE and RA patients were not. However, we found no association between PD1.3 polymorphism and the SLE or RA susceptibility, nor clinical or epidemiological data. Conclusion: There was no significant association between PD1.3 polymorphism and SLE or RA susceptibility in this Southern Brazilian population.

RESUMO Objetivo: Este estudo teve como objetivo analisar a relação entre o polimorfismo do gene PDCD1 (programmed cell death 1) (PD1.3G/A - rs11568821) com características do lúpus eritematoso sistêmico (LES) e da artrite reumatoide (AR) em uma população do sul do Brasil. Métodos: A técnica de PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Lenght Polymorphism) foi utilizada para analisar amostras de 95 pacientes com LES e 87 com AR, assim como em 128 indivíduos do grupo controle de Santa Catarina, sul do Brasil. Foi analisada a probabilidade de equilíbrio de Hardy-Weinberg (EHW) e a odds ratio (OR), considerando um IC 95% e p ≤ 0,05. Resultados: As frequências alélicas PD1.3 A foram de 0,095 (LES), 0,115 (AR) e 0,078 (controles). Os genótipos do grupo controle estavam em EHW, enquanto aqueles dos pacientes com LES e AR não estavam. No entanto, não foi encontrada associação entre o polimorfismo PD1.3 e a suscetibilidade ao LES ou à AR, nem com dados clínicos ou epidemiológicos. Conclusão: Não foi encontrada associação significativa entre o polimorfismo PD1.3 e a susceptibilidade ao LES ou à AR nessa população do sul do Brasil.

Association of PDCD1 polymorphism to Systemic Lupus Erythematosus and Rheumatoid Arthritis susceptibility. / Associação entre o polimorfismo do gene PDCD1 e a susceptibilidade ao lúpus eritematoso sistêmico e à artrite reumatoide.

OBJECTIVE: This study aims to analyze the relationship of programmed cell death 1 (PDCD1) gene polymorphism (PD1.3G/A - rs11568821) with features of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in a Southern Brazilian population. METHODS: Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) was performed in 95 SLE and 87 RA patients and 128 control group individuals from Santa Catarina, Southern Brazil. The Hardy-Weinberg Equilibrium (HWE) test, and odds ratio (OR) were analyzed, considering CI 95% and p≤0.05. RESULTS: The PD1.3A allele frequencies were 0.095 (SLE), 0.115 (RA) and 0.078 (controls). The genotypes of the control group were in HWE, while those of SLE and RA patients were not. However, we found no association between PD1.3 polymorphism and the SLE or RA susceptibility, nor clinical or epidemiological data. CONCLUSION: There was no significant association between PD1.3 polymorphism and SLE or RA susceptibility in this Southern Brazilian population.

Frecuencia del polimorfismo PD-1.3 del gen del receptor de muerte celular programada 1 (PD-1) y su asociación con diabetes tipo 1 / Frequency of polymorphism PD-1.3 of programmed cell death 1 (PD-1) and their association with type 1 diabetes

Background: The programmed cell death 1 (PDCD-1) immune-receptor is a key element in the negative regulation of peripheral tolerance in T cells. The gene has several polymorphisms and can be associated with susceptibility to autoimmune diseases. Aim: To analyze the frequency and distribution of PD-1.3 polymorphism of PDCD-1 gene and explore its possible contribution as a susceptibility gene for type 1 diabetes (T1D). Patients and Methods: We analyzed 248 cases with T1D with recent diagnosis and 160 control children under 15 years of Santiago. Genetic polymorphism in PD-1 gene variant for PD-1.3 (rs 11568821) was analyzed by polymerase chain reaction and restriction fragment length polymorphism. Comparison of genotype, allele frequency and consistency with respect to Hardy-Weinberg were analyzed using X2 tests and Fisher exact test. Results: There was a very low frequency of the genotype A/A, both in T1D patients and in controls (< 2 percent). The A/G genotype was more common in diabetic patients than in controls (41.6 and 18.8 percent respectively, p < 0.04). G/G genotype was more common in controls than in patients (79.4 and 56.8 percent respectively, p < 0.02). T1D patients carrying genotype G/G had a higher frequency of anti-GAD65 and anti-A-2 antibodies (81 and 67 percent respectively). Conclusions: The distribution of PD-1.3 genotype frequencies are similar to that reported elsewhere. Possibly, this genetic variant (rs 11568821) does not have an important marker role in Chilean T1D patients.