Functional gene polymorphisms in aggressive and chronic periodontitis

There is strong evidence that genetic as well as environmental factors affect the development of periodontitis, and some suggestion that aggressive and chronic forms of the disease share the same genetic predisposition. This study addresses the hypothesis that there are both shared and unique genetic associations in these forms of periodontitis. A sample of 51 patients with aggressive disease, 57 patients with chronic disease, and 100 healthy controls was recruited for this study. Ten functional polymorphisms in 7 candidate genes were genotyped. The results show statistically significant (p 相似文献   

雌激素受体基因多态性与慢性牙周炎相关性研究

目的探讨雌激素受体基因多态性与陕西地区慢性牙周炎易感性的关联。方法收集陕西地区109例慢性牙周炎患者和99例牙周健康对照组的颊黏膜拭子,用Chelex-100方法提取全基因组DNA, 用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术检测雌激素α和β受体基因型分布。结果慢性牙周炎组与正常对照组在ER-α受体XbaⅠ基因型分布上有统计学差异,慢性牙周炎组XX型基因频率明显高于正常对照组,尤其在女性患者中此差异显著,男性患者中未见不同;ER-β受体RsaⅠ和AluⅠ基因型在患者组与对照组中分布未见差异。结论慢性牙周炎易感性与雌激素XbaⅠ基因型分布相关,汉族女性群体中ER-α受体XX基因型可能为慢性牙周炎的易感因子。     

Matrix metalloproteinase levels in children with aggressive periodontitis

BACKGROUND: Matrix metalloproteinases (MMPs) are a family of host-derived proteinases reported to mediate multiple functions associated with periodontal destruction and inflammation. Most of the existing data have been gathered from adults with chronic periodontitis. The purpose of this study was to determine the MMP levels in a cohort of African American children with and without aggressive periodontitis. METHODS: Gingival crevicular fluid (GCF) was collected in a cohort of 44 African American children, 7 to 19 years of age, with and without aggressive periodontitis (AgP) and compared to healthy unrelated children and to adults with chronic periodontitis (CP). GCF volume was determined with a calibrated gingival fluid meter. The samples were assayed for MMP-1, -2, -3, -8, -9, -12, and -13 using fluorimetric substrates. RESULTS: The MMP levels from diseased sites in the subjects with AgP were statistically higher (P <0.05) in almost all instances than those associated with the unrelated controls or with the subjects with CP. MMP-8 was significantly elevated in the diseased sites of the children with AgP relative to non-diseased sites in the same children (P = 0.002), as well as the siblings, non-diseased controls, and subjects with CP (P < or =0.0001). There was no positive correlation between probing depth and any MMP level. CONCLUSIONS: MMP levels were elevated in AgP sites relative to non-diseased sites in the same subjects, in siblings, and in unrelated controls. MMPs associated with the AgP sites in children were generally elevated compared to an adult cohort with a history of CP.     

Membrane type (MT) 1-matrix metalloproteinase (MMP) and MMP-2 expression in ligature-induced periodontitis in the rat

BACKGROUND: Matrix metalloproteinases (MMPs) have been shown to be involved in the degradation of the extracellular matrix (ECM). In particular, MMP-2 and MMP-9 (gelatinase A and gelatinase B, respectively) have been identified as the predominant MMPs during periodontitis. Recent studies have indicated that a novel transmembrane MMP, mebrane-type 1 matrix metalloproteinase (MT1-MMP), can activate pro-MMP-2 in tumor metastasis. This study aims to elucidate the presence and localization of MT1-MMP and MMP-2 in periodontitis in a rat model. METHODS: In 2 groups of 40-day-old male Sprague-Dawley rats, periodontitis was initiated by ligating floss around maxillary second molars. A group of control animals were left untreated. Maxillary dentoalveolar segments were isolated after 7 and 21 days postinduction and were prepared for gross and radiographic analysis of bone loss and for histological analysis. Samples were also prepared for gel zymography to detect the presence of MMP-2, and for Northern blot analysis and in situ hybridization with MT1-MMP probes. RESULTS: MMP-2 expression increased at 21 days following ligature placement, in conjunction with MT1-MMP expression. MT1-MMP mRNA expression was observed in epithelial cells, fibroblasts, and in multinucleated cells in the periodontium. CONCLUSION: Our data suggest that MT1-MMP may play a role in extracellular matrix degradation during periodontitis, in concert with MMP-2 and other proteinases.     

C反应蛋白基因多态性与慢性牙周炎的相关性研究

目的 研究中国汉族人群中C反应蛋白(C-reactive protein,CRP)+1444C/T、CRP+1059G/C两种基因多态性与慢性牙周炎的关系,为进一步探讨CRP在牙周炎与冠状动脉粥样硬化性心脏病相关性中的作用和意义提供依据.方法 检测126例慢性牙周炎患者(CP组)和113名牙周健康或龈炎者(对照组)的牙周临床指数(附着丧失、探诊深度和探诊出血)、CRP水平及CRP+1059G/C、CRP+1444C/T基因多态性分布情况.结果 CP组中CRP+1059C等位基因的频率为6.7%(17/252);对照组4.9%(11/226),CP组与对照组之间的基因型分布和等位基因频率的分布差异均无统计学意义(0.250.5).结论 CRP+1059G/C、+1444C/T基因可能是CRP的功能性基因,尽管牙周炎与心血管疾病显著相关且CRP+1059G/C、+1444C/T与心血管疾病有相关性,但是这两个基因位点可能对中国汉族人群牙周炎患者的血清CRP水平影响不显著.     

C反应蛋白基因多态性与慢性牙周炎的相关性研究

Objective To investigate the relationship between C-reactive protein (CRP) + 1444C/T, CRP + 1059G/C polymorphisms and chronic periodontitis ( CP ) in a Han Chinese population. Methods Clinical periodontal parameters[ attachment loss( AL) probing depth(PD) and bleeding on probing(BOP) ] , and serum CRP levels were examined in CP patients (re = 126) and healthy subjects ( n = 113). Results The mean serum CRP level [ (1. 74 ± 1. 67) mg/L] was significantly higher in the CP group than in the control group [ (0. 57 ± 0. 39) mg/L] , P < 0. 001. In the control group, serum CRP levels were significantly lower in subjects with the CRP + 1059 GC and CC genotypes than those with the CRP +1059 GG genotype (P < 0.01). There was no significant difference between genotypes in the CP group. In CP and the control groups, serum CRP levels were significantly higher in subjects with the CRP + 1444 CT and TT genotypes compared to those with the CRP + 1444 CC genotype (P <0. 5). The percentage of CRP + 1059 C allele was 6. 7% (17/252) in the CP group and 4. 9% (11/226) in the control group. The percentage of CRP + 1444 T allele was 6. 3% (16/252) in the CP group and 5. 3% (12/226) in the control group (P > 0. 5). There was no significant difference between groups in both allele frequencies (P > 0. 5 ). The association of CRP + 1059G/C, CRP + 1444 C/T polymorphisms with CP was not found in a regression model ( P > 0. 5). Conclusions The presence of a CRP + 1059C-allele was associated with lower serum CRP levels and the presence of a CRP + 1444T-allele was associated with higher serum CRP levels. However, the data suggested that CRP + 1059G/C, CRP + 1444 C/T polymorphisms were not significantly associated with serum CRP levels of chronic periodontitis patients in ethnic Han Chinese.     

C反应蛋白基因多态性与慢性牙周炎的相关性研究

Objective To investigate the relationship between C-reactive protein (CRP) + 1444C/T, CRP + 1059G/C polymorphisms and chronic periodontitis ( CP ) in a Han Chinese population. Methods Clinical periodontal parameters[ attachment loss( AL) probing depth(PD) and bleeding on probing(BOP) ] , and serum CRP levels were examined in CP patients (re = 126) and healthy subjects ( n = 113). Results The mean serum CRP level [ (1. 74 ± 1. 67) mg/L] was significantly higher in the CP group than in the control group [ (0. 57 ± 0. 39) mg/L] , P < 0. 001. In the control group, serum CRP levels were significantly lower in subjects with the CRP + 1059 GC and CC genotypes than those with the CRP +1059 GG genotype (P < 0.01). There was no significant difference between genotypes in the CP group. In CP and the control groups, serum CRP levels were significantly higher in subjects with the CRP + 1444 CT and TT genotypes compared to those with the CRP + 1444 CC genotype (P <0. 5). The percentage of CRP + 1059 C allele was 6. 7% (17/252) in the CP group and 4. 9% (11/226) in the control group. The percentage of CRP + 1444 T allele was 6. 3% (16/252) in the CP group and 5. 3% (12/226) in the control group (P > 0. 5). There was no significant difference between groups in both allele frequencies (P > 0. 5 ). The association of CRP + 1059G/C, CRP + 1444 C/T polymorphisms with CP was not found in a regression model ( P > 0. 5). Conclusions The presence of a CRP + 1059C-allele was associated with lower serum CRP levels and the presence of a CRP + 1444T-allele was associated with higher serum CRP levels. However, the data suggested that CRP + 1059G/C, CRP + 1444 C/T polymorphisms were not significantly associated with serum CRP levels of chronic periodontitis patients in ethnic Han Chinese.     

Association of matrix metalloproteinase (MMP-1, MMP-3 and MMP-9) and cyclooxygenase-2 gene polymorphisms and their proteins with chronic periodontitis

Aims

The objective of this study was to investigate the association amongst the single nucleotide polymorphisms of genes encoding for matrix metalloproteinase (MMP) 1, 3, 9 and cyclooxygenase-2 (COX-2) of subjects. Protein production of MMPs, COX-2 and Vascular Endothelial Growth Factor (VEGF) were also investigated.

Methods

280 chronic periodontitis patients and 250 periodontitis-free subjects were selected. DNA was extracted from blood samples of all patients, the polymorphic sites of the genes that encode for metalloproteinases and cyclooxygenase-2 were amplified using PCR, and digested with restriction enzymes. ELISA was used to determine the protein production of MMPs, COX-2 and VEGF.

Results

The mean probing depth (PD) was 5.4 mm and the clinical attachment loss (CAL) was 6.4 mm in patients group with at least 2 years history. 2G/2G genotype of MMP-1, the periodontitis patients presented frequency of 28% and the control only showed 3%. 5A/5A genotype of MMP-3, the periodontitis patients presented higher frequency of 55% than the control 40%. C/C of genotype MMP-9, the periodontitis patients presented higher frequency of 51% than the control 17%. C/C of genotype COX-2, the periodontitis patients demonstrated 28% frequency and the control was 3%. ELISA analysis determined a significant difference (p < 0.001) in protein production between patient and control samples for the bio-markers. 12 cases with suspicious genotype of MMPs and in COX-2 showed the serum level was the highest value between other C/C genotype.

Conclusions

Combine genotype and serum expression of inflammatory mediators that may be a good bio-marker for diagnosis and prognosis of the periodontitis.     

Association of IL1 gene polymorphisms with chronic periodontitis in Brazilians

Chronic periodontal disease (PD) is an infectious immune-inflammatory illness. Polymorphisms in IL1 genes play a role in inflammatory diseases through the modulation of cytokine levels.

Objective

This study aimed to investigate the association between polymorphisms in the IL1 gene cluster and chronic periodontitis in a Brazilian population.

Design

A sample of 113 subjects over 25 years (mean age 41.2) were grouped into: 44 healthy individuals, 31 subjects with moderate and 38 with severe periodontitis. DNA was obtained through a mouthwash and oral mucosa scraping. PCR-RFLP was used to identify the following polymorphisms: IL1A C − 889T (rs1800587), IL1B C − 511T (rs16944), IL1B C + 3954T (rs11436340), IL1RN intron 2 (rs2234663). Differences in the allele/genotype/haplotype frequencies were assessed by Chi-square test (p < 0.05). The risk associated with alleles, genotypes and haplotypes was calculated as odds ratio (OR) with 95% confidence intervals (CI).

Results

Neither IL1A (C − 889T) nor IL1B (C + 3954T) polymorphisms was associated with chronic PD. Allele T for IL1B (C − 511T) only associated with PD in the group of blacks and mulattos. Moreover, genotype 2/2 for IL1RN (intron 2) was associated with severe PD.

Conclusions

Genotype 2/2 of IL1RN for the whole Brazilian population and allele T of IL1B (C − 511T) in a subgroup of Afro-Americans and mulattos were suggested as putative risk indicators for chronic periodontitis.     

Interleukin 10 gene promoter polymorphisms are associated with chronic periodontitis

BACKGROUND: Chronic periodontitis (CP) is characterized by an inflammation in the supporting tissues of the teeth caused primarily by bacterial infection. Interleukin 10 (IL10) is an anti-inflammatory cytokine whose genetic polymorphisms may influence the expression of the protein. Objective: In this study we investigated the hypothesis that single-nucleotide polymorphisms (SNPs) in the promoter of IL10 gene might be related to CP. MATERIALS AND METHODS: DNA was obtained from n=67 CP patients and n=43 control subjects. All studied individuals were non-smokers. The -1087 SNP was investigated by DNA sequencing, and the -819 and -592 SNPs by restriction fragment length polymorphism of PCR products. RESULTS: Frequencies of -819 and -592 SNPs showed differences between the control and CP groups. The ACC haplotype was more prevalent in the control group and the ATA haplotype more prevalent in the CP group. The ATA haplotype seemed to increase susceptibility to CP in women (odds ratio (OR)=2.57). The heterozygous haplotype GCC/ACC was predominant in the control group (OR=8.26; p=0.001). CONCLUSIONS: Specific haplotypes and SNPs in IL10 gene are associated with susceptibility to CP in Brazilian patients.     

Prevalence of OPG and IL-1 gene polymorphisms in chronic periodontitis

AIM: To investigate the association of polymorphisms in the osteoprotegerin (OPG) and interleukin 1 (IL-1) genes with chronic periodontitis (CP). MATERIAL AND METHODS: One hundred and ninety-four individuals (97 CP patients, 97 controls) were genotyped for the OPG polymorphisms Lys3Asn and Met256Val and for the IL-1 polymorphisms IL-1A (-889C/T) and IL-1B (+3953C/T). RESULTS: The homozygous variants coding for Lys3 were present at a higher frequency, whereas Asn3 and Met256 were present at a lower frequency in CP patients/controls (Lys3: 31%/25%, Asn3: 23%/32% and Met256: 66%/73%). Heterozygosity for Lys3Asn was observed at a higher frequency in CP patients/controls (46%/43%). Homozygosity for the Val256 genotype was observed in two CP patients (one in controls). Met256Val heterozygosity was more prevalent in CP patients/controls (32%/20%). All differences were statistically not significant between CP patients and controls. In contrast, both IL-1 polymorphisms were statistically significant. The heterozygous variant for IL-1A was present in 32% of the CP patients and in 20% of the controls (homozygosity (patients/controls) CC: 10%/21% and TT: 55%/33%). Heterozygosity for IL-1B was observed in 37% of the CP patients versus 34% in the controls (homozygosity (patients/controls) CC: 26%/57% and TT: 37%/9%). CONCLUSION: While the association between the IL-1 polymorphisms and CP was confirmed, no association between the OPG polymorphisms and CP could be found.     

慢性重度牙周炎的CD14受体基因多态性研究

目的研究慢性重度牙周炎的发生、发展的遗传学倾向,探讨CD14受体基因中-159位点c-t多态性及-1359位点g-t多态性与慢性重度牙周炎的相关情况。方法选择发病组患者和对照组健康者,应用聚合酶链反应-限制性片断长度多态(PCR-RFLP)技术,测定慢性重度牙周炎患者CD14受体基因的多态分布并对它们与慢性重度牙周炎患者的相互关系进行探讨。结果①CD14受体基因中-159位点c-t的基因多态分布与慢性重度牙周炎患者无关联(P>0.05)。②CD14受体基因中-1359位点g-t的基因多态分布与慢性重度牙周炎患者有关联(P<0.05)。结论CD14受体基因中g(-1359)t的多态位点是慢性重度牙周炎患者的风险因子。     

Renin–angiotensin gene polymorphisms in relation to severe chronic periodontitis

Aim: Evidence suggests that the ultimate product of the renin–angiotensin system (RAS), angiotensin II, exerts inflammatory actions. The present study aimed to evaluate the inter‐relation between gene polymorphisms of the RAS components; angiotensin converting enzyme (ACE), angiotensinogen (AGT) and angiotensin II type‐I receptor (AT1R), and severe chronic periodontitis (CP). Material and Methods: DNA was obtained from peripheral blood of 90 CP patients and 126 periodontally healthy subjects, and the clinical parameters were recorded. ACE I/D, AGT M235T and AT1R A1166C polymorphisms were genotyped by the PCR–RFLP method. Chi‐square, anova and logistic regression methods were used in statistical analyses. Results: The frequency of the ACE D allele was significantly lower in the CP group than the healthy group (p_corr=0.015). CP subjects exhibited increased C allele carriage and C allele frequency of the AT1R gene (p_corr=0.03 and p_corr=0.03, respectively). All clinical parameters of CP patients were found to be similar in variant allele‐carrying and non‐carrying subjects (p>0.05). Conclusions: The present findings suggest that ACE I/D and AT1R polymorphisms might be associated with susceptibility to CP but not with disease severity. The D allele of ACE I/D might be associated with decreased, whereas the C variant of AT1R A1166C might be associated with an elevated risk for CP in Turkish population.     

Association of interleukin-10 gene polymorphisms with severe generalized chronic periodontitis

BACKGROUND: Interleukin-10 (IL-10), an anti-inflammatory cytokine, plays a role in periodontal disease by inhibiting synthesis of proinflammatory cytokines and stimulating protective antibody production. Genetic polymorphisms in the IL-10 gene might be useful as a marker to diagnose susceptibility to periodontitis. Therefore, the aim of this study was to investigate the association between IL-10 gene polymorphisms and severe generalized chronic periodontitis (CP) in a Turkish population. METHODS: Samples of venous blood and DNA were obtained from 75 patients with severe generalized CP and 73 healthy subjects. The IL-10 promoter sequences at positions -597 and -824 were amplified by polymerase chain reaction, and polymorphisms were detected by restriction enzyme cleavage. Genotype and allele frequencies were calculated, and data were analyzed using the chi(2) test. Results: There was a statistically significant difference in frequencies of genotypes (AA/CC + CA: P = 0.00007, odds ratio = 12.37, 95% confidence intervals = 2.74 to 7.77; CC/CA + AA: P = 0.001, odds ratio = 3.05, 95% confidence intervals = 1.47 to 6.33) and alleles (P = 0.0002, odds ratio = 2.61, 95% confidence intervals = 1.52 to 4.51) at position -597 C to A between patients with severe generalized CP and healthy controls, whereas there was no significant difference in genotypes and allele frequencies at position -824 C to T between patients with CP and healthy subjects. CONCLUSION: Within the limitations of sample selection and number, the IL-10 gene polymorphism at position -597 seems to be associated with severe generalized CP.     

Association of interleukin-10 gene promoter polymorphisms with chronic and aggressive periodontitis

Oral Diseases (2012) 18 , 271–279 Objective: Interleukin‐10 gene promoter polymorphisms have been associated with interleukin‐10 decreased production, thereby playing a role in the pathogenesis of periodontitis. This study aimed to investigate whether interleukin‐10 single nucleotide polymorphisms at positions ‐1087(G/A) and ‐597(C/A) are associated with generalised chronic periodontitis and localised aggressive periodontitis. Methods: Genomic DNA samples were isolated from 276 unrelated Jordanian participants. Subjects were categorised into 86 periodontally healthy controls, 105 chronic periodontitis patients and 85 localised aggressive periodontitis patients. Genotype frequencies were calculated, and differences were determined using Pearson chi‐squared test, and odds ratio and 95 % confidence intervals were included. Results: The frequencies of the ‐1087A and ‐597A alleles were significantly more common in chronic periodontitis patients than controls. The A‐positive allele genotypes (GA, AA) at position ‐1087 and A‐positive allele genotypes (CA, AA) at position ‐597 appeared to increase the risk of having chronic periodontitis. No significant differences were observed in the genotype frequencies between localised aggressive periodontitis patients and controls. Conclusions: These findings indicate the possible use of interleukin‐10 single nucleotide polymorphisms as genetic markers in chronic periodontitis patients and further emphasise the molecular differences between chronic periodontitis and aggressive periodontitis.