RESUMEN
Periodontitis (PD) is a chronic inflammatory process resulting from the relationship of the immune response with the components in dental plaque. Cytokines and their genetic polymorphisms seem to be involved in the immunopathogenesis of this disease. This study aimed to evaluate the correlation of IL16 polymorphism with PD. A case-control study was conducted in a sample of individuals from southern Brazil. The genotyping of IL16, rs11556218 T>G, rs4072111 C>T e rs4778889 T>C, was performed using the PCR-RFLP methodology. The serum level of IL-16 was determined using an IL-16 ELISA kit for humans. SNPStats and OpenEpi software and Wilcoxon's U test were used to perform statistical analysis. IL16 rs11556218 polymorphism was significantly associated to PD in nonsmoking patients: individuals with G/G genotype were less likely to develop PD compared to the T/T genotype (OR = 0.10; Pc = 0.019, codominant model). In addition, the TTT haplotype was associated with a high risk for PD (OR = 2.45; P = 0.01). A low IL-16 serum level was observed among individuals with PD when compared to controls (P = 0.027). Thus, the IL16 rs16556218 polymorphism and the serum levels of IL-16 were associated with periodontitis in a Brazilian sample, and this was influenced by environmental factors such as smoking.
Asunto(s)
Predisposición Genética a la Enfermedad , Interleucina-16/genética , Periodontitis/genética , Fumar/epidemiología , Adulto , Brasil/epidemiología , Estudios de Casos y Controles , Femenino , Genotipo , Técnicas de Genotipaje , Haplotipos , Humanos , Interleucina-16/sangre , Masculino , Persona de Mediana Edad , Periodontitis/sangre , Periodontitis/epidemiología , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Fumar/efectos adversosRESUMEN
The pathogenesis of periodontitis (PD) involves several molecules of the immune system that interact in a network to eliminate the periodontopathogens, yet, they contribute to periodontal tissue destruction. The different mechanisms that lead to periodontal tissue damage are not clear. Despite this, immune response genes have been related to the development of PD previously, such as those involved in inflammasomes which are multiprotein complexes and cytokines including Interleukin-1. The aim of the study was to evaluate the polymorphisms in NLRP3 inflammasome, cytokine and receptor of cytokines genes in the development of periodontitis. This case-control study was conducted in 186 patients with PD (stage II and III and grade B) and 208 controls (localized gingivitis and periodontally healthy individuals). Genotyping was performed using PCR-RFLP for the SNP rs4612666 in NLRP3 and using PCR-SSP for IL1A, IL1B, IL1R, IL1RN, IL4RA, INFG, TGFB1, TNF, IL2, IL4, IL6, and IL10. Cytokine serum levels were measured using Luminex technology. SNPStats and OpenEpi software were used to perform statistical analysis. The higher frequencies of NLRP3 T/C and IL1B -511 T/T genotypes and IL2 (+166, -330) GT haplotype were observed in patients with PD compared to controls. The SNPs in NLRP3, IL1R +1970, IL6-174, TNF -308, IL2 +166 and -330, TGFB1 +869 and +915, IL4RA +1902, IL4-1098 and -590 were associated to PD in men. In conclusion, polymorphisms in NLRP3, IL1B and IL2 genes were associated to PD susceptibility. Men carrying the NLRP3, IL1R, IL6, TNF, IL2, TGFB1, IL4RA and IL4 polymorphisms had greater susceptibility than women for developing PD.
Asunto(s)
Interleucina-1beta/genética , Interleucina-2/genética , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Periodontitis/genética , Adulto , Citocinas/genética , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos/genética , Humanos , Inflamasomas/genética , Masculino , Persona de Mediana Edad , Periodontitis/patología , Polimorfismo de Longitud del Fragmento de Restricción/genética , Polimorfismo de Nucleótido Simple/genética , Caracteres Sexuales , Factor de Crecimiento Transformador beta1/genéticaRESUMEN
The pathogenesis of periodontitis involves a complex interaction between the microbial challenge and the host immune response. The individual immunoinflammatory response has a great contribution in the pathogenesis of the disease and becomes a trigger in the process of bone remodeling which is a characteristic of the disease. Thus, the aim of this study was to evaluate the influence of the TLR4 A896G (rs4986790), TLR4 C1196T (rs4986791), CD14 C-260T (rs2569190), RANKL (TNFSF11, rs2277438), and OPG (TNFSF11B C163T, rs3102735) polymorphisms in periodontitis. A case-control study was conducted on patients with periodontitis (N = 203) and controls (N = 213) over 30 years of age, without diabetes mellitus, acute infections, and osteoarthritis, and patients without aggressive periodontitis, i.e., stage IV and C degree of periodontitis, and any periodontal treatment performed in the last 6 months. Genotypes were determined by the PCR-RFLP and sequencing method. The frequency comparisons between case and controls were performed using the chi-square test and logistic regression (OpenEpi and SNPStats software). The risk (OR) was evaluated for values of P < 0.05. Differences in TLR4, CD14, RANKL, and OPG genotype and allele frequency distributions were not observed between patients and controls. However, some variants were a risk factor for the development of periodontitis when considering gender and smoking habits. The TLR4 896 A/G genotype was a risk factor for periodontitis in males (OR = 2.86), and the TLR4 1196C/C genotype was a risk factor for nonsmoking males (OR = 1.85) when compared to women. The RANKL A/A and the OPG T/C genotype was associated with the risk of the disease in nonsmoking men compared to nonsmoking women with the same genotype (OR = 1.96 and OR = 2.9, respectively). In conclusion, TLR4, CD14, RANKL, and OPG variants were not associated with periodontitis. However, TLR4, RANKL, and OPG polymorphisms could be a risk for periodontitis in males regardless of smoking habits.
Asunto(s)
Receptores de Lipopolisacáridos/metabolismo , Osteoprotegerina/metabolismo , Periodontitis/genética , Periodontitis/metabolismo , Polimorfismo Genético/genética , Ligando RANK/metabolismo , Receptor Toll-Like 4/metabolismo , Adulto , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes/genética , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Receptores de Lipopolisacáridos/genética , Masculino , Persona de Mediana Edad , Osteoprotegerina/genética , Ligando RANK/genética , Receptor Toll-Like 4/genéticaRESUMEN
Genetic variations contribute to the susceptibility in the development of periodontitis. The aim of this study was to investigate the influence of IL18, IL12, and MMP9 polymorphisms in the chronic periodontitis. This case-control study involved 381 individuals matched by gender and age. Genotyping of IL18 (rs187238 and rs1946518) and IL12B (rs3212227) was performed by PCR-SSP and PCR-RFLP was used for MMP9 (rs3918242). IL-18 and MMP-9 were quantified in the serum by ELISA. SNPStats and OpenEpi software were used for statistical analysis and, in order to eliminate smoking as a confounding factor, the analyses were also performed in nonsmoking subjects. The IL18-137G/C genotype was associated with the risk of chronic periodontitis in nonsmokers (P c = 0.03; OR = 1.99; overdominant inherence model). In the multivariate analyses, homozygous IL18-137G/G and IL18-607C/C were more frequent in males compared to women with these same genotypes (OR = 2.51 and OR = 3.30, respectively). The serum levels of the IL-18 in patients were higher than those in healthy controls (P = 0.005). IL12B and MMP9 polymorphisms and MMP-9 serum concentration were similar in patients and controls. In this study, IL18 was associated with chronic periodontitis susceptibility. Men had greater risk than women for developing the disease when IL18 polymorphism was considered and the susceptibility was independent of the smoking status.
Asunto(s)
Subunidad p40 de la Interleucina-12/genética , Interleucina-18/genética , Metaloproteinasa 9 de la Matriz/genética , Periodontitis/genética , Fumar/genética , Adulto , Pueblo Asiatico , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Longitud del Fragmento de Restricción/genética , Polimorfismo de Nucleótido Simple/genética , Regiones Promotoras Genéticas/genéticaRESUMEN
Polycystic ovary syndrome (PCOS) affects the endocrine system and is associated with low-grade inflammation. Natural killer (NK) cells are involved in the defense of the female reproductive tract, folliculogenesis, ovulation and the menstrual cycle. The killer-cell immunoglobulin-like receptors (KIR) on the surface of NK cells modulate the activation and function of these cells after interacting with human leukocyte antigen (HLA) class I ligands. The objective of this study was to evaluate the possible association of the KIR and their HLA ligands with polycystic ovary syndrome. METHODS: Ninety-three patients with PCOS according to the Rotterdam criteria and 104 healthy controls were included in this study. The HLA class I and KIR genotypes were determined using a PCR-SSO technique, rSSO Luminex®. In order to assess whether the distribution of the HLA and KIR genotypes was in Hardy-Weinberg equilibrium, Arlequin 3.1 software was used. The frequency distributions in the two study groups were compared using the chi-squared statistic with Yates´s correction using Open Epi software. RESULTS: The higher frequencies of KIR3DS1-Bw4 (41% vs. 19%, Pc = 0.002; OR = 2.90) and homozygotic KIR2DS4-del (54% vs. 26%, Pc = 0.0002; OR = 3.316) in patients compared with controls suggest they confer susceptibility to PCOS. A lower frequency of KIR2DS4-full was observed in patients (43% vs. 70%, Pc = 0.0004, OR = 0.320). CONCLUSION: KIR and its HLA ligands were associated with the development of PCOS in the studied population.
Asunto(s)
Predisposición Genética a la Enfermedad , Células Asesinas Naturales/inmunología , Síndrome del Ovario Poliquístico/genética , Receptores KIR3DS1/genética , Receptores KIR/genética , Adulto , Estudios de Casos y Controles , Epítopos/genética , Epítopos/inmunología , Femenino , Frecuencia de los Genes , Técnicas de Genotipaje , Antígenos de Histocompatibilidad Clase I/inmunología , Antígenos de Histocompatibilidad Clase I/metabolismo , Homocigoto , Humanos , Células Asesinas Naturales/metabolismo , Síndrome del Ovario Poliquístico/inmunología , Receptores KIR/inmunología , Receptores KIR3DS1/inmunología , Adulto JovenRESUMEN
In this study, were genotyped 22 single nucleotide polymorphisms (SNPs) in 13 genes that encode the pro-inflammatory (IL-1α, IL-1ß, IL-1R, IL-4Rα, IL-12, IFN-γ, TNF-α, and IL-2) and anti-inflammatory (IL-1RA, TGF-ß, IL-4, IL-6 and IL-10) cytokines of 350 individuals by PCR-SSP (polymerase chain reaction - sequence specific primer). A total of 473 individuals were genotyped for IL17A and IL17F genes by PCR-RFLP (restriction fragment length polymorphism). The sample consisted of healthy and unrelated subjects from a mixed population from Parana state, in the South region of Brazil. The frequency analyses and genotype data are available in the Supplementary materials and are accessible at Allele Frequency Net Database (AFND).
Asunto(s)
Citocinas/genética , Genotipo , Inflamación/genética , Interleucina-17/genética , Brasil , Bases de Datos Genéticas , Frecuencia de los Genes , Humanos , Polimorfismo Genético , Polimorfismo de Longitud del Fragmento de RestricciónRESUMEN
A case-control study was conducted on patients with chronic periodontitis (CP) and healthy controls with the aim of evaluating possible association between interleukin 17A (IL17A) G197A (rs2275913) and IL17F T7488C (rs763780) polymorphisms and periodontitis. Genotypes were determined by PCR-RFLP method. Statistical analyses were conducted using the OpenEpi and SNPStas software to calculate Chi-square with Yates correction or Fisher's exact tests, odds ratios (OR), and 95% confidence intervals (CIs). SNPStas software was used to calculate Hardy-Weinberg equilibrium. IL17A AA genotype was more frequent in patients with chronic periodontitis (CP) in the codominant and recessive models (P = 0.09; OR = 2.53 and P = 0.03; OR = 2.46, resp.), the females with CP (P = 0.01, OR = 4.34), Caucasoid patients with CP (P = 0.01, OR = 3.45), and nonsmoking Caucasian patients with CP (P = 0.04, OR = 3.51). The IL17A A allele was also more frequent in Caucasians with CP (P = 0.04, OR = 1.59). IL17F T7488C polymorphism was not associated with chronic periodontitis. In these patients from Southern Brazil, the IL17A rs2275913 polymorphisms, IL17A AA genotype, and the A allele were associated with a susceptibility to chronic periodontitis.