SINGLE NUCLEOTIDE POLYMORPHISMS IN IL-1A
RS1800587, IL-1B RS1143634 AND VITAMIN D RECEPTOR
RS731236 IN STAGE III GRADE B/C PERIODONTITIS
Özturk Özener H.1, Tacal Aslan B.2, Eken B.F.2, Agrali Ö.B.1,
Yildrim H.S.1, Altunok E.Ç.3, Ulucan K.2, Kuru L.1
*Corresponding Author: Assist. Prof. Dr. Hafize Öztürk Özener, Address: Marmara University, Faculty
of Dentistry, Department of Periodontology Basıbuyuk, Maltepe, Istanbul, Turkey. Fax number: +90 216
421 02 21; E-mail: hafize.ozturk@marmara.edu.tr
page: 10
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DISCUSSION
Recent evidence has shown that, with the continuous
advancement of genetic engineering technology,
gene polymorphism can be an important basis for the individual
differences in the development and progression
of periodontitis. In this study, the frequencies of IL-1A
(rs1800587), IL-1B (rs1143634) and VDR (rs731236) gene
polymorphisms were evaluated for the first time in Stage
III Grade B/C periodontitis patients in comparison with
periodontally healthy individuals. Among different genotyping
methods, Real-time PCR that could rapidly and
simultaneously detect SNPs was preferred in this study.
SNPs from the promoter region, which play an essential
role the transcriptional regulation in the coding region,
can affect the expression of a gene. The genes in IL-1 family
possess allele polymorphisms in which SNP -889C/T
(rs1800587) in IL-1A gene and SNP +3654 (rs1143634) in
IL-1B gene are researched extensively. Our findings revealed
that the genotypic distributions of IL-1A (rs1800587) and
IL-1B (rs1143634) gene polymorphisms are not associated
with Stage III periodontitis. These results are consistent with
the previous studies reporting no relationship between SNPs
rs1800587 or rs1143634 and neither chronic nor aggressive
periodontitis [8,27-33]. On the other hand, contradictory
findings were published declaring significant associations
between either of the two SNPs and periodontal diseases [29,
34-39]. Majumder et al. [40] and Wagner et al. [41] concluded
that IL-1A (rs1800587) polymorphism was related to the susceptibility
of chronic periodontitis. Recently, a meta-analysis
of ethnicity assessment revealed that IL-1A (rs1800587) gene
polymorphism is associated with an increased risk of chronic
periodontitis in Europeans, US Americans and Africans, but
not in Algerians and Mexicans [42]. The results of the present
study displayed T allele for IL-1B (rs1143634) to be associated
with the periodontitis patients, while the C allele was
associated with the healthy individuals. Similarly, T allele
in IL-1B (+3954C/T) was linked to high risk of periodontal
disease in Asians, Caucasians, and in mixed populations,
however not in Africans [14]. Considering that these differences
may be related to the population, the literature contains
no data on the Turkish population regarding IL-1A (-889C/T)
and only 2 research studies have been published about IL-1B
(+3954C/T). Yücel et al. [43] stated that the distribution of
allele and genotype frequencies for IL-1B (+3954C/T) were
similar among chronic periodontitis, aggressive periodontitis
and healthy control groups. On the other hand, our result was
contrary to the results of Güzeldemir et al. [37] who show
that susceptibility to localized aggressive periodontitis is
increased by homozygosity for allele 1 of rs1143634 which
referred to (C→T) at position +3954 in the fifth exon of the
IL-1B gene. In the new classification, localized aggressive
periodontitis may refer to the Stage III or IV and Grade C. It
is thought that different outcomes can be obtained depending
on the size (31 healthy subjects and 31 localized aggressive
periodontitis patients) and the different status of the patients
based on the new classification of periodontal diseases.
The VDR, a ligand-controlled transcription factor,
intervenes the actions of the vitamin D hormone 1,25-dihydroxyvitamin
D3 to alter bone mineral homeostasis.
VDR TaqI gene polymorphism is positioned at exon 9. The
current study demonstrated that increased TT genotype
and T allele of the VDR TaqI polymorphism in healthy
subjects were associated with the decreased risk of periodontitis.
Similar to the present study, De Brito et al. [19]
reported that the patients with any form of C (formerly t)
allele (Tt or tt genotypes) were 2.4 times more susceptible
to chronic periodontitis than the patients who lacked C
allele. However, Gunes et al. [44] contradicted this finding
and suggested that TaqI polymorphisms of the VDR
gene were not associated with severe generalized chronic
periodontitis in the Turkish population studied. In two
meta-analyses published in 2011 [21] and 2012 [22], no
association was observed in the Caucasian population,
while chronic, but not aggressive, periodontitis cases, in
patients among the Asian population were reported to have
a weak, significantly higher frequency of the TT genotype
and T allele of TaqI. The findings of a recently published
meta-analysis, in contrast with the above meta-analyses,
reveal a link between periodontitis susceptibility and the
VDR TaqI polymorphism in Caucasian patients under the
dominant model without any apparent correlation in Asian
participants [45]. The frequency TaqI alleles may vary
among different populations. It has been shown that the T
allele frequency of the VDR TaqI polymorphism is lowest
among Asians, about of the 8% population, and highest in
Caucasians, at 43% [46]. The genetic susceptibility of a
subject to periodontitis due to polymorphism might change
on account of the ethnicity of the population.
Genetic factors are of great importance in identifying
the host’s immune response to infection and could account
for significant variation in the severity, distribution, and
extension of the disease [47-49]. The grade of periodontitis
is predicted by direct or indirect evidence of the progression
rate of in three levels: Grade A (slow progression), Grade
B (moderate progression) and Grade C (rapid progression)
[2]. With the given facts, the present study investigated
whether SNPs rs1800587, rs1143634 and rs731236 might
be related with the progression of periodontal disease in
a group of the Turkish population. In our study, healthy
individuals and Grade B and Grade C Stage III periodontitis
patients were evaluated and compared. T allele of the
rs1143634 was linked to patients having Grade B Stage III
periodontitis. Our finding was in accordance with da Silva et al. [14], who revealed that T allele of the rs1143634 was
related with an increased risk of periodontal disease in
Asians, Caucasians and in a mixed population. The outcome
of the present study demonstrated that rs731236 (TaqI)
polymorphism is significantly associated with Grade B
Stage III periodontitis, but not Grade C, in comparison
with healthy individuals. In the assessment of associations
between the grading of periodontitis and gene polymorphism,
TaqI polymorphism CT genotype is higher in Grade
B periodontitis patients. In a research study conducted
by Chantarangsu et al. [50], with a homogeneous Thai
population, the VDR gene polymorphism was examined
according to the severity of chronic periodontitis (no/mild,
moderate and severe). The study revealed that there is no
relationship between TaqI and periodontitis. To the authors’
knowledge, this is the first study evaluating susceptibility to
periodontitis according to Grade and Stage approach in the
classification of periodontitis. A limitation of our study may
be the absence of other stages or grades of periodontitis.
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