Association between Periodontitis, Genetic Polymorphisms and Presence of Coronary Artery Disease in Southern Brazil / Relação entre Periodontite, Polimorfismos Genéticos e Doença Arterial Coronariana no Sul do Brasil

Abstract Background: Periodontitis and coronary artery disease (CAD) share an inflammatory etiology; there is a recent concern regarding the investigation of an association between these two conditions. Current theories indicate that cytokines and proteins have an important role in this process. C-reactive protein and interleukin-6 are inflammatory derivatives produced in the presence of periodontitis and in the pathophysiology of coronary disease. The polymorphisms of CRP + 1444 C > T and IL6-174 G > C are recognized in the literature as being related to CAD. Objective: This study investigates the association between periodontitis and coronary artery disease, through the presence of PCR and IL-6 polymorphisms. Methods: We selected 80 patients who underwent diagnostic catheterization in the HU of UFSM. The presence of periodontitis was determined by the Community Periodontal Index, whereas the CAD was established by the medical report. DNA was collected from a saliva sample and the presence of polymorphism was determined by PCR and restriction enzymes. A significance level of 5% was adopted. Results: The mean age of all participants (p = 0.035, OR 2.65; 95%CI: (1.02-6.87) male gender (p = 0.012, OR 3.37; 95% CI: (1.28- (p = 0.013, OR 3.66; 95% CI: (1.27-10.5)), PCR polymorphism + 1444C > T (p = 0.001, OR 6.37; 95% CI:, (2.25-17.9)) and IL6 -174 G > C polymorphism (p = 0.025, OR 2.87, 95% CI: (1.09-7.55)) were statistically associated with the presence of CAD. Age > 60 years and presence of the PCR +1444 C > T polymorphism remained independently associated with CAD after adjustment by logistic regression. Conclusions: The presence of the PCR + 1444 C > T polymorphism in this study was independently associated with the presence of coronary artery disease.

Resumo Fundamento: A periodontite e a doença arterial coronariana (DAC) compartilham uma etiologia inflamatória. Existe preocupação na investigação de associação entre essas duas condições. Há citocinas e proteínas com papel importante neste processo, como a proteína C-reativa (PCR) e a interleucina 6 (IL-6), que são derivados inflamatórios produzidos na presença da periodontite e na fisiopatologia da DAC. Os polimorfismos da PCR+1444 C > T e da IL-6 -174 G > C são reconhecidos na literatura como relacionados à DAC. Objetivo: Este estudo objetiva comprovar a associação entre periodontite e DAC, através da presença dos polimorfismos da PCR e da IL-6. Métodos: Foram selecionados 80 pacientes que se submeteram ao cateterismo diagnóstico no Hospital Universitário da Universidade Federal de Santa Maria (UFSM). A periodontite foi determinada pelo índice periodontal comunitário; a DAC, pelo laudo médico. Foi coletado o ácido desoxirribonucleico (DNA) pela saliva e estabelecido o polimorfismo pela avaliação da PCR/RFLP. Foi adotado um nível de significância estatística de 5%. Resultados: A idade mediana de todos os participantes (p = 0,035; OR 2,65; IC 95% [1,02-6,87]), gênero masculino (p = 0,012; OR 3,37; IC 95% [1,28-8,9]), periodontite (p = 0,013; OR 3,66; IC 95% [1,27-10,5]), polimorfismo da PCR +1444 C > T (p = 0,001; OR 6,37; IC 95% [2,25-17,9]) e polimorfismo da IL-6 -174G > C (p = 0,025; OR 2,87; IC 95% [1,09-7,55]) foram estatisticamente relacionados à DAC. Após ajuste com a regressão logística, mantiveram-se independentemente associadas à DAC a idade maior que 60 anos e o polimorfismo da PCR +1444 C > T. Conclusões: O polimorfismo da PCR +1444 C > T, neste estudo, esteve independentemente relacionado à DAC.

Association of leptin and leptin receptor polymorphisms with coronary artery disease in a North Chinese Han population

Abstract INTRODUCTION: Leptin (LEP) is a peptide hormone that acts via leptin receptor (LEPR) binding. Genetic evidence from different human populations has implicated LEP/LEPR in the pathogenesis of coronary artery disease (CAD), and suggests that certain LEP/LEPR gene polymorphisms may increase the risk of CAD. The aim of this study was to assess two single nucleotide polymorphisms (SNPs) in LEP genes (rs2167270 and rs7799039) and two in LEPR genes (rs6588147, rs1137100) for association with CAD. METHODS: We enrolled 271 North Chinese Han CAD patients, and 113 healthy age- and sex-matched controls. Genomic DNA was extracted from whole blood, and the four SNPs were assessed using a MassArray system. RESULTS: The G allele frequency at rs2167270 was significantly higher among CAD cases than among controls. The AG genotype at rs7799039 was associated with a significantly decreased risk of CAD unlike the AA genotype used as the reference. The A allele was significantly associated with the CAD patient group. Interestingly, statistically significant differences in genotype and allele frequency at LEP rs2167270 and rs7799039 existed among females but not among males. CONCLUSIONS: The current study detected a significant association between genetic variations at LEP rs7799039 and rs2167270 and the risk of CAD in a north Chinese population, and revealed that LEP rs2167270 and rs7799039 gene polymorphisms might act as predisposing factors for CAD.

Diagnostic value of circulating lncRNA ANRIL and its correlation with coronary artery disease parameters

This study aimed to detect the expression of the long non-coding RNA (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) and evaluate its correlation with disease risk, stenosis degree, inflammation, as well as overall survival (OS) in coronary artery disease (CAD) patients. A total of 230 patients who underwent diagnostic coronary angiography were consecutively recruited and assigned to CAD group (n=125) or control group (n=105) according to presence or absence of CAD. Gensini score was calculated to assess the severity of coronary artery damage. Plasma samples were collected and the expression ANRIL was detected in all participants. High-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), and cytokines including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-8, IL-10, and IL-17 in CAD patients were measured and OS was calculated. The relative expression of ANRIL was higher in CAD patients compared to controls (P<0.001). Receiver operating characteristic disclosed that ANRIL could distinguish CAD patients from controls with an area under the curve of 0.789 (95%CI: 0.731-0.847). Spearman's rank correlation test revealed that expression of ANRIL was positively correlated with Gensini score (P=0.001), levels of hs-CRP (P=0.001), ESR (P=0.038), TNF-α (P=0.004), and IL-6 (P<0.001), while negatively correlated with IL-10 level (P=0.008) in CAD patients. Kaplan-Meier curve revealed that high expression of ANRIL was associated with shorter OS (P=0.013). In conclusion, circulating ANRIL presented a good diagnostic value for CAD, and its high expression was associated with increased stenosis degree, raised inflammation, and poor OS in CAD patients.

Serum Klotho (but not haplotypes) associate with the post-myocardial infarction status of older adults

OBJECTIVES: The number of deaths from vascular diseases is incredibly high worldwide, and reliable markers for major events are still needed. The current cross-sectional study investigated the association of Klotho haplotypes and Klotho serum levels with classic risk factors and a clinical history of vascular events. METHODS: Clinical, anthropometric, biochemical and nutritional assessments were conducted with 168 older adults, complemented by genotyping (rs9536314 and rs9527025) and the detection of serum Klotho (ELISA). RESULTS: Klotho levels and haplotypes did not associate with most classic risk factors for vascular events, including markers such as C-reactive protein and homocysteine. A positive association was only found between Klotho levels and the previous occurrence of a myocardial infarction by both correlational (p=0.006) and variance analyses (p<0.001), and these associations were independent of the context. CONCLUSION: Our results suggest that serum Klotho is higher in individuals with a clinical history of myocardial infarction but not with a history of coronary artery disease or stroke. None of the Klotho haplotypes were associated with the variables investigated herein.

Associations between CD36 gene polymorphisms and susceptibility to coronary artery heart disease

Associations between polymorphisms of the CD36 gene and susceptibility to coronary artery heart disease (CHD) are not clear. We assessed allele frequencies and genotype distributions of CD36 gene polymorphisms in 112 CHD patients and 129 control patients using semi-quantitative polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Additionally, we detected CD36 mRNA expression by real-time quantitative PCR, and we quantified plasma levels of oxidized low-density lipoprotein (ox-LDL) using an enzyme-linked immunosorbent assay (ELISA). There were no significant differences between the two groups (P>0.05) in allele frequencies of rs1761667 or in genotype distribution and allele frequencies of rs3173798. The genotype distribution of rs1761667 significantly differed between CHD patients and controls (P=0.034), with a significantly higher frequency of the AG genotype in the CHD group compared to the control group (P=0.011). The plasma levels of ox-LDL in patients with the AG genotype were remarkably higher than those with the GG and AA genotypes (P=0.010). In a randomized sample taken from patients in the two groups, the CD36 mRNA expression of the CHD patients was higher than that of the controls. In CHD patients, the CD36 mRNA expression in AG genotype patients was remarkably higher than in those with an AA genotype (P=0.005). After adjusted logistic regression analysis, the AG genotype of rs1761667 was associated with an increased risk of CHD (OR=2.337, 95% CI=1.336-4.087, P=0.003). In conclusion, the rs1761667 polymorphism may be closely associated with developing CHD in the Chongqing Han population of China, and an AG genotype may be a genetic susceptibility factor for CHD.

Homocistéina e metilenotetrahidrofolato redutase em indivíduos submetidos à angiografia coronariana / Homocysteine and methylenetetrahydrofolate reductase in subjects undergoing coronary angiography

OBJETIVO: Determinar os níveis plasmáticos de homocisteína e a incidência do polimorfismo C677T no gene da enzima metilenotetrahidrofolato redutase (MTHFR) em um grupo de indivíduos submetidos a angiografia coronariana, buscando estabelecer a possível correlação entre esses parâmetros e a gravidade da doença arterial coronariana (DAC), bem como investigar a correlação entre hiper-homocisteinemia e a presença do polimorfismo. MÉTODOS: Vinte indivíduos com ausência de ateromatose nas coronárias (controles), quatorze indivíduos apresentando ateromatose leve/moderada e vinte e nove indivíduos apresentando ateromatose grave foram avaliados. RESULTADOS: Para o parâmetro homocisteína foram observadas diferenças significativas entre as médias dos grupos controle e ateromatose grave (p < 0,001). Entre os demais grupos não foram observadas diferenças significativas. O grupo ateromatose grave apresentou uma freqüência de 62,0 por cento e 6,9 por cento para o polimorfismo C677T no gene da enzima MTHFR, em heterozigose e homozigose, respectivamente. Entretanto, não foi observada correlação entre a presença da mutação e hiper-homocisteinemia. Foi observada uma correlação positiva da ordem de 41,91 por cento (p < 0,001) entre hiper-homocisteinemia e a presença de DAC. CONCLUSÃO: O achado mais importante deste estudo foi a associação entre hiper-homocisteinemia e a presença de estenose coronariana superior a 70 por cento; entretanto, permanece a dúvida se o aumento da concentração plasmática de homocisteína constitui um fator determinante para o agravamento da lesão aterosclerótica nas coronárias ou se o mesmo é uma conseqüência desta lesão.

OBJECTIVE: To determine plasma homocysteine levels and the incidence of methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism in a group of subjects who underwent coronary angiography, in an attempt to establish a correlation between these parameters and the severity of coronary artery disease (CAD), as well as investigate the correlation between hyperhomocysteinemia and the presence of polymorphism. METHODS: Twenty subjects with no coronary atheromatosis (controls), fourteen subjects with mild/moderate atheromatosis, and twenty-nine subjects with severe atheromatosis were evaluated. RESULTS: Significant differences were observed in mean homocysteine levels between the control and the severe atheromatosis groups (p < 0.001). No significant differences were observed among the other groups. The severe atheromatosis group showed rates of 62.0 percent and 6.9 percent for the C677T MTHFR gene polymorphism, in heterozygous and homozygous subjects, respectively. However, there was no correlation between the presence of mutation and hyperhomocysteinemia. A positive correlation of 41.91 percent (p < 0.001) was found between hyperhomocysteinemia and CAD. CONCLUSION: The most important finding of this study was the association between hyperhomocysteinemia and coronary stenosis > 70 percent; yet, whether elevated plasma homocysteine worsens atherosclerosis or is a consequence remains to be established.