Effect of gene polymorphisms on periodontal diseases

Periodontal diseases are inflammatory diseases of supporting structures of the tooth. It results in the destruction of the supporting structures and most of the destructive processes involved are host derived. The processes leading to destruction and regeneration of the destroyed tissues are of great interest to both researchers and clinicians. The selective susceptibility of subjects for periodontitis has remained an enigma and wide varieties of risk factors have been implicated for the manifestation and progression of periodontitis. Genetic factors have been a new addition to the list of risk factors for periodontal diseases. With the availability of human genome sequence and the knowledge of the complement of the genes, it should be possible to identify the metabolic pathways involved in periodontal destruction and regeneration. Most forms of periodontitis represent a life-long account of interactions between the genome, behaviour, and environment. The current practical utility of genetic knowledge in periodontitis is limited. The information contained within the human genome can potentially lead to a better understanding of the control mechanisms modulating the production of inflammatory mediators as well as provides potential therapeutic targets for periodontal disease. Allelic variants at multiple gene loci probably influence periodontitis susceptibility.     

Cigarette smoking enhances T cell activation and a Th2 immune response; an aspect of the pathophysiology in periodontal disease

Smoking is a strong risk factor for periodontitis. Treated patients who smoke show increased risk for further periodontal breakdown, despite receiving maintenance care. Previous work indicated that such patients have a monocytic cytokine response favoring Th2 activity. The purpose of this study was to investigate the T lymphocytic cytokine production representing Th1 and Th2 subpopulations in smokers and non-smokers. Venous blood was collected from 30 treated periodontitis patients (12 smokers) and 24 healthy subjects (12 smokers). Whole blood cell cultures were stimulated and interferon (IFN)-γ and interleukin (IL)-13 were measured in the culture supernatants, representing types 1 and 2 Th subpopulations, respectively. Unadjusted data showed that smokers had more lymphocytes, and higher levels of IFN-γ and IL-13, irrespective of being periodontal patient. However in a multivariate analysis, increased IFN-γ production was not significantly explained by smoking, while higher IL-13 was strongly explained by smoking (21%, p < 0.001). We suggest that the increased Th activity and specifically an elevated Th2 profile in smokers may constitute a risk for smoking patients which may induce conversion of periodontal stability into progressive disease. This phenomenon may be equally important in other conditions, where connective tissue and bone loss are hallmarks of disease pathophysiology.     

Proinflammatory cytokines production and PMN-elastase release from activated PMN cells in the periodontal disease

The aim of this study was to evaluate the local changes in the crevicular gingival fluid (CGF) determined by the inflammatory and immune response in periodontitis and gingivitis. The selected patients presented gingivitis (n = 9) and periodontitis: aggressive periodontitis (n = 21) and adult periodontitis (n = 8). The crevicular fluid was provided from the gingival and periodontal pocket. The measurement of PMN-elastase in the CGF, using the ELISA method, showed a significant (p < 0.01) increase of the enzyme concentration in the aggressive periodontitis group (62.1 +/- 3.91 ng/ml) comparing to the gingivitis group (33.04 +/- 4.14 ng/ml) but also the increase (p < 0.05) of this enzyme in the adult periodontitis (43.6 +/- 2.16 ng/ml) comparing to the gingivitis, which indicated the evolutive aspects of the inflammatory reaction in these diseases. The increased production of PMN-E is the result of the activation of polymorphonuclear cells (PMN) as a reaction of the microbial attack. Degranulation and release of proteolytic enzymes including elastase, which present cytotoxic capacities, follow the activation of neutrophil granulocytes (PMN). The activated granulocytes release proinflammatory cytokines IL-1, TNF-alpha which augment the inflammatory immune response. The aggressive periodontitis group showed an increased CGF level of IL-1 (780.4 +/- 104 pg/ml) comparing to the gingivitis group (275.5 +/- 78 pg/ml) (p < 0.01). TNF-alpha also presented an increased level (p < 0.01) in the aggressive periodontitis group (16.3 +/- 2.3 pg/ml) comparing to the gingivitis group (4.1 +/- 1.2 pg/ml) as a consequence of the periodontium destruction and of the tissular necrosis in the former group. In conclusion, our study shows a significant increase of the PMN-elastase and proinflammatory cytokines level in CGF of patients with gingivitis and periodontitis. The intensity of the inflammatory response in these diseases is strongly correlated to the activation of the neutrophil granulocytes which release these biological active molecules that could be used as evolution markers of the disease.     

Berberine as a promising natural compound for the treatment of periodontal disease: A focus on anti-inflammatory properties

Accumulating evidence during the last two decades has addressed the potential anti-inflammatory properties of berberine (BBR), a bioactive alkaloid compound isolated from Coptidis rhizoma, in controlling or treating several inflammatory diseases. Periodontitis is one of the most common chronic and serious inflammatory diseases, in which uncontrolled and unabated host immune responses against periodontopathic pathogens play critical and crucial roles in the disease pathogenesis. Hence, regulating inflammatory responses in periodontitis has a valuable approach and holds promise in treating periodontitis. For the first time, this paper reviews the evidence from in vitro and in vivo experimental models to explore the anti-inflammatory effects of BBR in periodontitis and exhibits that BBR has the high potency to exert anti-inflammatory effects by reducing expression and secretion of pro-inflammatory mediators including TNF-α, IL-1β, IL-17, RANKL, MMP-2, MMP-9 and MCP-1. The BBR-mediated anti-inflammatory actions could translate into the inhibition of the periodontal tissues and alveolar bone destruction and the control of the disease in vivo. As the second aim of this paper, we also paid attention to the therapeutic potential of BBR in treating human diseases regarding its anti-inflammatory properties.     

Interleukin-12 and interleukin-16 in periodontal disease

The immune system plays an important role in the pathological process of periodontitis. Interleukin-12 (IL-12) is produced by monocytes, macrophages and neutrophils. These cells are proinflammatory infiltrates in periodontitis tissues. High IL-12 will contribute to the immune reaction to Th1 type. IL-12 is an inducer of INF-r production. IFN-gamma itself can also activate IL-12 production. Lipopolysaccharides (LPS) of periodontopathogens are also activators of IL-12. Interleukin-16 (IL-16) can cause the high affinity of IL-2 receptors on CD4+ cells and is chemotaxis to Th1 cells and CD4+ T cells. IL-16 can stimulate monocytes to produce proinflammatory cytokines and is highly associated with inflammation including arthritis, enteritis and allergic rhinitis. However, the information on IL-12 and IL-16 in periodontitis is not clear. In this study, 105 GCF samples were collected from 19 periodontal disease patients and 6 healthy ones. The clinical periodontal indices, the habits of cigarette smoking and alcohol drinking were recorded. ELISA was used to determine the levels of IL-12 and IL16 in the GCF. In the non-smoking/non-alcohol-drinking individuals: (1) the total amount of IL-12 (but not IL-16) was significantly higher in chronic periodontitis (CP) sites than gingivitis (G) or healthy (H) sites; (2) the diseased sites (CP + G) had a significantly higher total amount of IL-12 (but not IL-16) than the H sites. Among CP sites, both the concentration and total amount of IL-16 (but not IL-12) were significantly higher in alcohol drinkers/cigarette smokers as compared to the non-drinkers/non-smokers. CP sites of the drinkers/smokers also had significantly deeper probing pocket depth than sites of those without these two habits. IL-12 and IL-16 may be related to the pathogenesis of periodontal disease, but within the periodontitis sites, IL-16 may be related to disease severity in alcohol drinkers/smokers.     

Comparison of an oxidative stress biomarker "urinary8-hydroxy-2'-deoxyguanosine," between smokers and non-smokers

A great deal of effort has been made on the effect of oxidative stress for smokers. What seems to be lacking, however, is its evidence. Analyzing 1076 participants (age 35.9 +/- 12.9, urinary8-OHdG Mean +/- S.D., 11.4 +/- 6.7, n = 1076), our study found the significant increase in a biomarker of DNA damage urinary 8-OHdG/creatinine among smokers (7.75 +/- 2.8 ng/ml x CRE (n = 154) and 7.36 +/- 2.5 ng/ml x CRE (n = 627) (p < 0.05), Relative Risk = 2.9 (1.4-6.2) sex and age +/- 2 matching 105 male smokers and non-smokers. There was no significance on the comparison between female smokers and non-smokers. Smokers have significantly decreased serum alpha-tocopherol (1012 +/- 455, 1152 +/- 857, p < 0.03). The amount of serum ascorbate did not change. Smokers lowered serum HDL-cholesterol compared to non-smokers (59.3 +/- 11.8, 63.9 +/- 13.3, p < 0.05). The result of oxidative stress profile (OSP) also indicated that the increase of oxidative stress to smokers (p < 0.05). The calculated value of oxygen radical absorbance capacity (ORAC) of the meal for subjects was 1600 ORAC units.     

Distribution of salivary Lactobacillus and Bifidobacterium species in periodontal health and disease

We surveyed the distribution of salivary Lactobacillus and Bifidobacterium species in periodontitis patients and healthy subjects. Approximately 700 lactobacilli and 300 bifidobacterial isolates were obtained from 16 young, orally healthy subjects (mean age +/- standard deviation: 21.0+/-2.0 y), 16 periodontitis patients (51.6+/-13.8 y), and 14 well-maintained former periodontitis patients (60.2+/-9.6 y). Among eleven Lactobacillus species detected in saliva, L. salivarius, L. gasseri, and L. fermentum were prevalent, but no species was specifically associated with periodontal health. In contrast, of four Bifidobacterium species, B. adolescentis was specifically (P<0.05) prevalent in young healthy subjects compared with the other two groups. Furthermore, the bifidobacterial count of the well-maintained subjects was the highest (P<0.05) among the groups. These results suggest that bifidobacterial count and species might be associated with periodontal health status and/or age.     

Serum levels of oncostatin M (a gp 130 cytokine): an inflammatory biomarker in periodontal disease

Objective: Periodontitis is considered to be a risk factor for systemic diseases such as atherosclerosis, diabetes, etc., and cytokines play a key role. The present study was carried out to measure the level of serum oncostatin M (OSM) in patients with chronic periodontitis, and to evaluate the effect of non-surgical periodontal therapy on the serum OSM concentration.

Materials and methods: Sixty subjects were divided into three groups (each group n?=?20) based on the gingival index (GI), probing pocket depth (PPD) and clinical attachment level (CAL): group I healthy; group II gingivitis; and group III chronic periodontitis. Group III patients were followed for 8 weeks after non-surgical periodontal therapy as the after-treatment group (group IV). Estimation of serum OSM was done using an enzyme-linked immunosorbent assay.

Results: The mean OSM concentrations in serum were highest in the chronic periodontitis group (mean 68.05 pg ml^?1) and decreased following treatment (39.65 pg ml^?1) while OSM was undetectable in healthy subjects or in patients with gingivitis.

Conclusion: Increased serum OSM concentration in patients with chronic periodontitis and its positive correlation with PPD and CAL, suggest its role as an inflammatory biomarker in periodontal disease and it may exaggerate other systemic conditions such as atherosclerosis and rheumatoid arthritis.     

Subgingival microflora in smokers with early onset periodontitis

Cigarette smoking is a potent risk factor which has recently been associated with periodontal disease progression. The objective of this study was to detect the microbial profile of early onset periodontitis in smokers and compare it to that of non-smokers. The study population consisted of 50 systemically healthy individuals aged 25 to 38 years, exhibiting early onset periodontitis. 25 patients were smokers (> 20 cigarettes/day) and 25 non-smokers. Two pooled bacterial samples comprised of four periodontal sites with probing depth > 5 mm each, were collected from each individual. The samples were cultured aerobically and anaerobically for bacterial isolation using selective and non-selective media. Isolates were characterized to species level by conventional biochemical tests and various identification kits. The differences in bacterial counts using the Mann Whitney U test were statistically significant for Staphylococcus aureus, Campylobacter concisus, Eikenella corrodens, Escherichia coli, Bacteroides forsythus, Bacteroides gracilis, Campylobacter rectus, Porphyromonas gingivalis, Selenomonas sputigena and Candida albicans in smokers. Statistically significant differences for Peptostreptococcus micros, Actinomyces naeslundii, Eubacterium lentum and Capnocytophaga gingivalis were detected in non-smokers. The isolation of bacteria belonging to the exogenous flora like E. coli, C. albicans and S. aureus in smokers microflora underscores the importance of the host which is adversely affected by cigarette smoking.     

Salivary isoprostanes indicate increased oxidation injury in periodontitis with additional tobacco abuse

Isoprostanes (IPs) are indicators of in-vivo oxidative stress, and have been successfully used as markers for chronic inflammatory processes. The presence of chronic periodontal disease and cigarette smoking has been individually linked to the development of atherosclerosis, yet data regarding oxidative stress in this context are not available yet. The aim of this study was to evaluate levels of the salivary prostaglandins (PGs) 8-epi-PGF(2alpha), 6-oxo-PGF(1alpha), thromboxane B(2) (TXB(2)) and PGF(2alpha) in association with periodontal disease status with and without additional cigarette smoking. We analyzed saliva samples from 121 adults, (aged 21-73 years, 90 non-smokers, 31 smokers) for levels of 8-epi-PGF(2alpha), 6-oxo-PGF(1alpha), TXB(2) and PGF(2alpha). On the basis of periodontal disease indices the periodontal status of each subject was assessed and outcomes were then correlated with smoking status and laboratory findings. Salivary 8-epi-PGF(2alpha) levels increased with deteriorating plaque index, and were significantly higher (115.5 +/- 23.5 pg/ml) in smoking individuals, when compared to non-smokers (70.2 +/- 20.4 pg/ml, p<0.0001). In addition, smokers showed higher TXB(2) and PGF(2alphas) and lower 6-oxo-PGF(1alpha) levels p<0.0001). Oxidative stress, as reflected by elevated salivary 8-epi-PGF(2alpha) levels, is associated with the extent of periodontal disease and is significantly aggravated by concomitant tobacco abuse. Chronic inflammation and smoking have been individually associated with the development of atherosclerosis. The results of this study indicate that: 1) salivary IPs can reliably assess the degree of oxidative stress, and: 2) smoking and periodontal disease are two modifiable cardiovascular risk factors, able to potentiate each other.     

Salivary immunoglobulin classes in Nigerian smokers with periodontitis

AIM:To determine the levels of salivary immunoglobulin classes in Nigerian smokers and non-smokers with periodontitis.METHODS:Sixty-nine individuals were recruited into this study after obtaining informed consent.They were subdivided into three groups that consisted of 20(aged 46 ± 11 years) cigarette smokers with periodontitis(S+P);24(40 ± 12 years) smokers without periodontitis(S-P);and 25(53 ± 11 years) non-smokers with periodontitis(NS+P).An oral and maxillofacial surgeon used radiographs for periodontal probing for the diagnosis of periodontitis.The smokers included subjects who smoked at least six cigarettes per day and all the periodontitis patients were newly diagnosed.About 5 mL of unstimulated saliva was expectorated by each subject into plain sample bottles.Salivary immunoglobulin levels were estimated using enzyme linked immunosorbent assay.Student's t test was used to deter-mine significant differences between the means.Values of P 0.05 were regarded as significant.RESULTS:No significant differences were observed in the mean salivary levels of the immunoglobulin classes(IgG,IgA,IgM and IgE) when S+P was compared with S-P.Mean salivary levels of IgA(520.0 ± 155.1 ng/mL vs 670.0 ± 110 ng/mL,P = 0.000) and IgM(644.5 ± 160.0 ng/mL vs 791.4 ± 43.7 ng/mL,P = 0.000) were significantly lower in the S+P compared with NS+P group.Salivary IgA(570.4 ± 145.6 ng/mL vs 670.0 ± 110 ng/mL,P = 0.008) and IgM(703.1 ± 169.3 ng/mL vs 791.4 ± 43.7 ng/mL,P = 0.012) levels were significantly lower in the S-P compared with NS+P group.Only one(5%) periodontal patient had detectable levels of salivary IgE(0.20 IU/mL).Similarly,only one smoker(4.17%) had detectable levels of salivary IgE(0.04 IU/mL) and two non-smokers(9.52%) had detectable levels of IgE(0.24 IU/mL).CONCLUSION:Our study suggests that reduced salivary IgA and IgM levels in smokers with periodontitis could enhance increased susceptibility to periodontitis.     

Detection of Dialister pneumosintes in the subgingival biofilm of subjects with periodontal disease

Dialister pneumosintes has been indicated as a potentially new periodontopathic species. This study evaluated the prevalence of this microorganism in saliva and subgingival biofilm from subjects with different periodontal conditions. Subgingival biofilm and saliva samples from 48 subjects with periodontal health (PH) and 116 patients with chronic periodontitis (CP) were obtained. DNA was extracted from the samples and the presence of D. pneumosintes was determined by PCR. Differences in clinical parameters and frequency of D. pneumosintes between groups were sought by Mann-Whitney, Chi-square and Fisher's exact tests. Overall, D. pneumosintes was detected in 47.8% of the biofilm samples, but only in 3% of saliva samples. CP patients presented a significantly greater mean prevalence of this species in sites with periodontal health and periodontal infection (43.5+/-7.4% and 62.1+/-6.4%, respectively) than PH subjects (29.4+/-7.9%) (Mann-Whitney; p<0.01). Moreover, significant associations between the prevalence of D. pneumosintes and pocket depth (p=0.001), attachment loss (p=0.001) and bleeding on probing (GLM, p=0.014) were observed after adjusting for age and gender. These findings corroborate the association of D. pneumosintes with periodontitis.     

Levels of angiopoietins 1 and 2 in induced sputum supernatant in patients with COPD

Pathological features of chronic obstructive pulmonary disease (COPD) include lung vascular remodeling and angiogenesis. Angiopoietin-1 (Ang-1), is an essential mediator of angiogenesis by establishing vascular integrity, whereas angiopoietin-2 (Ang-2) acts as its natural inhibitor. We determined the levels of angiopoietins in sputum supernatants of patients with COPD and investigated their possible association with mediators and cells involved in the inflammatory and remodeling process. Fifty-nine patients with COPD, 25 healthy smokers and 20 healthy non-smokers were studied. All subjects underwent lung function tests, sputum induction for cell count identification and Ang-1, Ang-2, VEGF, TGF-β1, MMP-2, LTB4, IL-8, albumin measurement in sputum supernatants. Airway vascular permeability (AVP) index was also assessed. Ang-2 levels were significantly higher in patients with COPD compared to healthy smokers and healthy non-smokers [median, interquartile ranges pg/ml, 267 (147-367) vs. 112 (67-171) and 98 (95-107), respectively; p<0.001]. Regression analysis showed a significant association between Ang-2 levels and AVP index, VEGF, IL-8 and MMP-2 levels in COPD, the strongest being with VEGF. Our results indicate that induced sputum Ang-2 levels are higher in COPD compared to healthy smokers and healthy non-smokers. Moreover, Ang-2 is associated with AVP, IL-8, MMP-2, and VEGF, indicating a possible role for Ang-2 in the pathogenesis of the disease.     

Antisense-mediated inhibition of ICAM-1 expression: a therapeutic strategy against inflammation of human periodontal tissue

Periodontal diseases, such as gingivitis and periodontitis, are caused by a mixed infection by several types of bacteria in the dental plaque, causing a chronic inflammation of the gingival mucosa. Inflammatory processes in conjunction with immune responses to bacterial attacks are generally protective. In profound periodontitis, however, hyperresponsiveness and hypersensitivity of the immune system are counterproductive because of the destruction of the affected periodontal connective tissues. The intercellular adhesion molecule type 1 (ICAM-1) plays a key role in the onset and manifestation of inflammatory responses. Thus, inhibition of ICAM-1 expression could be of therapeutic relevance for the treatment of destructive periodontitis. Here, antisense oligonucleotides (AS-ON) directed against ICAM-1 suppress protein expression and mRNA levels specifically and effectively in primary human endothelial cells of different tissue origin. Moreover, downregulation of ICAM-1 expression is also observed in AS-ON-transfected inflamed gingival mucosal tissue of patients with periodontal diseases. This work strongly suggests exploiting the local topical application of ICAM-1-directed AS-ON as a therapeutic tool against inflammatory processes of the human gingiva.     

The in vitro life-span of human periodontal ligament fibroblasts

The in vitro life-span of human periodontal ligament fibroblasts (PDLF) was studied on clones from periodontium of teeth extracted due to periodontitis and dental caries (69 clones/192 individuals, aged 20-80 years) and from periodontium of teeth extracted for orthodontic reasons (23 clones/26 individuals, aged 15-19 years). In the primary cultures the ratio of the number of cells expressing senescence-associated beta-galactosidase (SA-beta-Gal) to the total number of cells is significantly larger in PDLF (92 clones; 11.1+/-4.9%) than in human gingival fibroblasts (GF) (10 clones; 0.5+/-0.1 %). The finite population doubling numbers (PD) of PDLF are not age-matched and the mean PD of PDLF (7.1+/-2.9) is significantly smaller than GF (28.5+/-3.2), IMR-90 (human lung fibroblasts, 5 clones; 44.3 +/- 2.2), and human osteoblasts (5 clones; 19.7+/-1.4). Comparing the ratio of the number of SA-beta-Gal positive cells to the total number of cells in primary culture, and the finite PD in PDLF cultures: 1) the ratio of 15-19 years old donor group is significantly smaller than in the other donor groups (20-29, 30-39, 40-49, 50-59 and 60-80 years old), and 2) there were no statistically significant differences among the 20-29, 30-39, 40-49 and 50-59 year old donor groups, and the 30-39, 40-49, 50-59 and 60-80 year old donor groups. These findings suggest that the in vitro life-span of PDLF is shorter than other fibroblasts in the connective tissues and that PDLF may undergo senescence in adult clones without relation to donor's age. There may be more aged fibroblasts in periodontium than in other tissues, such as gingiva and lung.     

Impaired phagocytosis in localized aggressive periodontitis: rescue by Resolvin E1

Resolution of inflammation is an active temporally orchestrated process demonstrated by the biosynthesis of novel proresolving mediators. Dysregulation of resolution pathways may underlie prevalent human inflammatory diseases such as cardiovascular diseases and periodontitis. Localized Aggressive Periodontitis (LAP) is an early onset, rapidly progressing form of inflammatory periodontal disease. Here, we report increased surface P-selectin on circulating LAP platelets, and elevated integrin (CD18) surface expression on neutrophils and monocytes compared to healthy, asymptomatic controls. Significantly more platelet-neutrophil and platelet-monocyte aggregates were identified in circulating whole blood of LAP patients compared with asymptomatic controls. LAP whole blood generates increased pro-inflammatory LTB4 with addition of divalent cation ionophore A23187 (5 μM) and significantly less, 15-HETE, 12-HETE, 14-HDHA, and lipoxin A(4). Macrophages from LAP subjects exhibit reduced phagocytosis. The pro-resolving lipid mediator, Resolvin E1 (0.1-100 nM), rescues the impaired phagocytic activity in LAP macrophages. These abnormalities suggest compromised resolution pathways, which may contribute to persistent inflammation resulting in establishment of a chronic inflammatory lesion and periodontal disease progression.     

Factors contributing to chromosome damage in lymphocytes of cigarette smokers

Cigarette smoking is generally believed to be responsible for a substantial number of human health problems. However, the causal relationship between smoking, the induction of biological effects and the extent of health problems among smokers have not been fully documented. Using the recently developed lymphocyte micronucleus (MN) assay, we have evaluated the chromosome aberration frequencies in 67 cigarette smokers and 59 matched non-smoking control subjects. We found that the mean MN frequency (per 100 cells) in the smokers was slightly higher than that found in the non-smokers (0.71 +/- 0.23 and 0.58 +/- 0.05 respectively; p less than 0.08). Factors which contribute to the expression of chromosome aberrations were also investigated. A significant age-dependent increase in MN frequencies was observed in both groups (p less than 0.05). Linear regression analysis showed that the age-dependent effects among smokers (r = 0.54; p less than 0.02) was further enhanced by cigarette consumption (r = 0.62; p less than 0.005). Consumption of low potency 'one-a-day' type multivitamins had no effect on MN frequencies in either sex of non-smokers and in the 1 male smoker who took multivitamins but vitamin intake consistently reduced the MN frequencies among female smokers. Using a challenge assay, fidelity of DNA repair was evaluated. Lymphocytes from both smokers and non-smokers were irradiated with single doses of 0 or 100 cGy of X-rays or with double doses of 100 cGy of X-rays each separated by 15 or 60 min (100/15 or 100/60). Chromosome translocation frequencies were consistently higher after irradiation in lymphocytes from smokers than in those from non-smokers. Statistically significant differences were detected when the cells were irradiated with the double doses of 100 cGy X-rays each separated by 60 min (p less than 0.05). These data suggest that lymphocytes from smokers made more mistakes in the repair of DNA damage than cells from non-smokers. Our studies provide new insights into the genotoxic effects of cigarette smoke and new information which may be useful for understanding the mechanisms for induction of health problems from smoking.     

Gene polymorphisms in pro-inflammatory cytokines are associated with systemic inflammation in patients with severe periodontal infections

The inflammatory response to chronic infections such as periodontitis may be central to the systemic implications of these diseases. This study examined the possible association between specific gene polymorphisms and the systemic inflammatory response in individuals suffering from severe generalized periodontitis. Ninety-four subjects with periodontitis were genotyped for polymorphisms in IL-1A (-889), IL-1B (-511, +3954), TNF-A (-308), IL-6 (-174) and TLR4 (-299, -399) genes. We found that the genotypes for IL-1A or IL-6 are associated with higher levels of serum IL-6 (P < 0.03) and serum CRP (P < 0.05), similarly the TNF-A genotype is associated with higher levels of serum IL-6 (P < 0.05) after correction for age, body mass index, gender, ethnicity and cigarette smoking. Systemic inflammatory responses are higher in severe periodontitis patients carrying rare alleles for functional inflammatory gene polymorphisms. These results suggest that cytokine genotypes are important determinants of the systemic inflammatory response in subjects with periodontitis. Genetic polymorphism therefore, may in part explain the reported association between periodontitis and systemic disease.