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| Year : 2009 | Volume
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| Issue : 1 | Page : 37-40 |
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| Analysis of the association between interleukin -1β (+3954) gene polymorphism and chronic periodontitis in a sample of the south Indian population |
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Gurumoorthy Kaarthikeyan1, Nadathur Doraisamy Jayakumar1, Ogoti Padmalatha1, Varghese Sheeja1, Malaippan Sankari1, Balakrisnan Anandan2
1 Department of Periodontics, Saveetha Dental College, 162 P.H Road, Velappanchavadi, Chennai 600 077, India
2 Department of Genetics, ALMPGIBMS, University of Madras, Taramani, Chennai 600 113, Tamil Nadu, India
Click here for correspondence address and email
| Date of Submission | 10-Jan-2008 |
| Date of Decision | 03-Apr-2008 |
| Date of Acceptance | 06-Aug-2008 |
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 Abstract | | |
Aim : The aim of this study was to determine the association between IL-1B (+3954) gene polymorphism and chronic periodontitis in a sample of the south Indian population.
Settings and Design: This study employed a cross-sectional design involving individuals from the state of Tamil Nadu in the southern part of India.
Materials and Methods : Genomic DNA was obtained from the white blood cells of 30 patients with chronic periodontitis (18 males and 12 females) and 31 healthy controls (20 males and 11 females). The age of the subjects ranged from 30 to 55 years old and all were non smokers. DNA was amplified using the polymerase chain reaction (PCR) with specific primers flanking the locus +3954 of IL-1β gene and analyzed by 3% agarose gel electrophoresis.
Statistical Analysis : A Chi-square test was used to determine the genotype distribution between the groups and the relative risk was estimated with a 95% confidence interval.
Results and Conclusion : The chronic periodontitis group displayed a higher percentage of T allele, even though it was not statistically significant. The relative risk analysis between genotypes showed that the risk was higher for the CT genotype compared with the CC genotype and the risk was significant. In conclusion, our data suggested that there was no significant association between IL-1β (+3954) gene polymorphism and chronic periodontitis in the south Indian population. Keywords: Allele, periodontitis, polymorphisms
How to cite this article:
Kaarthikeyan G, Jayakumar ND, Padmalatha O, Sheeja V, Sankari M, Anandan B. Analysis of the association between interleukin -1β (+3954) gene polymorphism and chronic periodontitis in a sample of the south Indian population. Indian J Dent Res 2009;20:37-40 |
How to cite this URL:
Kaarthikeyan G, Jayakumar ND, Padmalatha O, Sheeja V, Sankari M, Anandan B. Analysis of the association between interleukin -1β (+3954) gene polymorphism and chronic periodontitis in a sample of the south Indian population. Indian J Dent Res [serial online] 2009 [cited 2023 Jun 6];20:37-40. Available from: https://www.ijdr.in/text.asp?2009/20/1/37/49061 |
Periodontitis is a chronic inflammatory disease of multifactorial etiology. Although the presence of gram-negative bacteria is essential in initiating the periodontal destruction, several environmental and genetic factors contribute to the individual variation in the etiology and the course of the disease. [1],[2]
The pro inflammatory cytokine IL-1 stimulates the secretion of matrix metalloproteinases, immunoglobulin G2 (IgG2), and prostaglandin E2 (PGE2). [3] It also induces osteoclastic bone resorption. Vital functions such as immune cell recruitment, cell proliferation, tissue destruction, bone resorption, and vascular smooth muscle cell contraction are all affected by IL-1. [4],[5] IL-1 acts as a master or key cytokine in many chronic diseases such as rheumatoid arthritis, [6] Alzheimer's disease [7] , and periodontitis. [8]
Among the pro inflammatory cytokines, IL-1β is the most potent and pathogenic form. [9] The gene regulating the production of IL-1β is located on the chromosome 2q14.2.[10]
Other pro inflammatory cytokines such as IL-1α and TNFα also play a role in periodontal destruction; however, in general a lack of association between TNFα polymorphisms and periodontitis has been consistently reported.[11],[12]
Kornman, et al. demonstrated that the occurrence of IL-1α(-889) and IL-1β (+3954) polymorphisms was simultaneously associated with chronic periodontitis in Caucasians who were non smokers. [13] Armitage, et al. found no association in the Chinese population. [14] IL-1 polymorphisms were associated with chronic periodontitis in the Maharastrian ethnicity in India. [15]
As the frequency of many genetic alleles varies between distinct ethnic groups, the aim of this study was to determine the association of IL-1β (+3954) polymorphism and chronic periodontitis in a sample of the south Indian population.
| Materials and Methods | |  |
This study employed a cross-sectional design involving individuals from the state of Tamil Nadu in the southern part of India. A total of 61 individuals who reported to the Department of Periodontics, Saveetha Dental College, Chennai (Tamil Nadu) were included in this study. The subjects were stratified into a chronic periodontitis group (n=30) and a control group (n=31) based on the clinical examination of probing pocket depth, clinical attachment loss, bleeding on probing, and radiographic analysis. The patients in the chronic periodontitis group (18 males and 12 females) were 30 to 55 years old and exhibited inflammation, loss of clinical attachment, and loss of adjacent supporting bone as evidenced by radiographic examination. All patients in the chronic periodontitis group had >30% of teeth exhibiting a clinical attachment loss of ≥ 7mm. The control group participants (20 males and 11 females) were 30 to 55 years old and did not present a history of previous periodontal disease as determined by the absence of clinical attachment loss, gingival inflammation, and no sites with a probing depth >3mm. A detailed history of dental treatments, family history of periodontal diseases, smoking habits as well as general health concerns were obtained from the subjects. Except for the presence of periodontitis, the patients included in this study were systemically healthy. Smokers were excluded from this study [Table 1]. Both the patients and the control subjects belong to south Indian ethnicity; others were excluded from this study [Table 1]. Informed consent was obtained from all subjects.
Sample Collection and DNA Extraction
A total of 5 ml of venous blood was collected by vein puncture and dispersed into a sterile tube containing a pinch of EDTA. It was mixed thoroughly to avoid clot formation.
DNA isolation was done according to the modified Miller, et al. 1998 protocol. [16] First red blood cell (RBC) lysis was done using the buffer NH4Cl (0.155 M) and Tris base (0.17 M). White blood cell (WBC) lysis was done using Tris HCl (1 M), Disodium EDTA (0.5 M), NaCl (1 M), and double distilled water. A total of 500 µl of proteinase K and 200 µl of sodium dodecyl sulfate were added to the tube. It was incubated for 16 hours in a water bath at 37°C. A total of 1 ml of 6M NaCl was added and vigorously shaken for 30 seconds. The tube was centrifuged at 3000 rpm for 20 minutes and 4 ml of supernatant was transferred to another fresh tube. Double the volume of ice-cold ethanol was added and tilted once or twice. The DNA fibers were transferred to a 1.5 ml centrifuge tube and the DNA was dissolved in 200 µl of TE buffer. It was left at room temperature for 1 hour and the sample was stored at -20°C.
Polymerase Chain Reaction and Restriction Endonuclease Digestion
IL-1β (+3954) polymorphisms were assessed by polymerase chain reaction (PCR) amplification and digestion. The sequences of PCR primers were 5'- CTCAGGTGTCCTCG AAGAAATCAAA-3' and 5'-GCTTTTTTGCTGTGAGTCCCG -3' with a PCR product size of 194 bp. PCR was carried out in a total volume of 20 µl containing 2 µl of template DNA, a pre mixed buffer (10X assay buffer -2 µl, 50 mM MgCl 2 - 2 µl, dNTPs mix -1.5 µl, Taq polymerase-0.2 µl), and forward and reverse primers each of 0.3 µl. The remaining 12.9 µl were autoclaved double distilled water. The amplification conditions consisted of 94°C for 3 mins, followed by 35 cycles of 94°C for 30 seconds, 55°C for 35 seconds, and 72°C for 30 seconds. The run was terminated by final elongation at 72°C for 5 minutes. Amplification was performed in a Eppendorf Thermocycler. The products were digested with 5U of Taq I at 65°C for 4 hours and obtained 97+85+12 bp DNA products for allele C and 182+12 bp for allele T. The visualization was performed in a 3% agarose gel electrophoresis.
Statistical Analysis
Statistical analysis of data was performed using the SPSS version. The Chi-square test was used to compare the genotype distributions between the control and chronic periodontitis groups (d.f.=1). The relative risk between the genotypes was estimated with 95% confidence intervals. A P-value of < 0.05 was considered significant [Figure 1].
| Results | | |
The genotype and allele distributions of the IL-1B (+3954) polymorphism are shown in [Table 2]. There was no significant difference in the genotype distribution when comparing the control group with the chronic periodontitis group, although the CT genotype was more in the chronic periodontitis group. Similarly, no significant difference was found when allele distribution was estimated. The relative risk analysis between genotypes showed that the risk was more for CT genotypes compared with CC and it was significant. When other genotypes were compared, there were no significant results.
| Discussion | | |
The association of cytokine gene polymorphisms with chronic inflammatory diseases as reported by Duff, et al. [8] has enhanced the interest in identifying the gene polymorphisms associated with periodontitis. [17] Many studies have reported associations between cytokine gene polymorphisms and periodontitis in distinct populations. [13],[18],[19],[20],[21] The frequency of genetic alleles varies between different ethnic groups and several studies found contradictory results. Kornman, et al. found a significant association between composite genotype and periodontitis in Caucasians, [13] whereas Armitage, et al. found no association. [14] There are differences in the genetic makeup of the ethnic groups residing in India. [22] Thus, the analysis of gene polymorphisms in a sample of the south Indian population represents an important advance in the study of periodontal diseases in India.
Smoking is an important risk factor for the establishment of periodontitis; however, many studies have found that genetic association with chronic periodontitis was more evident when smokers were excluded. [13],[18],[19] The effect of smoking in periodontitis was strong, even in subjects who are not genetically susceptible to disease. Due to the small sample size and for the above-described reasons, we excluded smokers from our study.
In this study, we evaluated a polymorphism in the locus +3954 of the IL-1B gene in a sample of the south Indian population and found no significant association between the occurrence of polymorphism and chronic periodontitis. This finding is in accordance with that of Armitage, et al. who found no association in the Chinese population [14] and Anusaksathien, et al. who found similar results in the Thai population. [23] Kornman, et al. found an association between the composite genotype - IL-1α (-889) and IL-1β (+3954) and chronic periodontitis in non smoking Caucasians. It has been mentioned that genetic polymorphisms likely influence susceptibility to periodontitis through the accumulated effect of multiple polymorphisms. However, single polymorphisms have been associated with periodontitis, as reported by Gore, et al. [19] and Moreira, et al. [20] Our results did not indicate an evident association of this polymorphism with chronic periodontitis; although a higher frequency of CT genotype was detected in the periodontitis group, it was not statistically significant.
The relative risk estimation of our study showed that the CC genotype was a protective factor for chronic periodontitis compared with the CT genotype, which was statistically significant. This is in accordance with many studies. [13],[19],[20] However, when other genotypes were compared, there was no significant result.
The biological plausibility of IL-1β gene polymorphism in periodontal disease is that it directly influences cytokine secretion. An exacerbated expression of IL-1 could lead to higher inflammation and tissue destruction. The polymorphism of this gene in the locus +3954 has been associated with increased production of IL-1β. Homozygous individuals for the T allele produce an amount that is four times higher than that of IL-1β compared with individuals displaying the CC genotype.[24],[25] Studies showed there was an increase in the levels of IL-1β in the gingival crevicular fluid of patients with IL-1β polymorphism.[26],[27]
Thus, we conclude from this study that there is no significant association between IL-1β (+3954) gene polymorphism and chronic periodontitis in the south Indian population. The findings from our study question the usefulness of using allele 2 of IL-1β as a genetic marker for identifying the susceptibility to chronic periodontitis in the south Indian population. However, further studies using larger samples are required to firmly establish the results.
| Acknowledgment | | |
I would like to acknowledge Dr. G. Jayaraman PhD, Director, ALMPGIBMS and Dr. M. Karthikeyan for their guidance and help in throughout the course of this study.
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Correspondence Address:
Gurumoorthy Kaarthikeyan
Department of Periodontics, Saveetha Dental College, 162 P.H Road, Velappanchavadi, Chennai 600 077
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0970-9290.49061
[Figure 1]
[Table 1], [Table 2] |
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