Vitamin D receptor genetic polymorphisms are associated with oral lichen planus susceptibility in a Chinese Han population

doi:10.21203/rs.2.10415/v2

Download PDF

Research article

Vitamin D receptor genetic polymorphisms are associated with oral lichen planus susceptibility in a Chinese Han population

https://doi.org/10.21203/rs.2.10415/v2

This work is licensed under a CC BY 4.0 License

Journal Publication

published 30 Jan, 2020

Read the published version in BMC Oral Health →

You are reading this older preprint version

Read the latest preprint version →

Vitamin D receptor ( VDR ) is involved in multiple immune-mediated disorders including oral lichen planus (OLP). This study investigated the association between VDR gene polymorphisms and the risk of OLP. In total, 177 OLP patients and 207 healthy participants were recruited from the Affiliated Hospital of Stomatology, Nanjing Medical University. Eight single nucleotide polymorphisms (SNPs: rs731236, rs739837, rs757343, rs2107301, rs2239185, rs7975232, rs11574129 and rs11568820) in the VDR gene were selected and genotyped. The results showed that OLP risk was increased in subjects with the rs2239185 TT genotype (Recessive model: adjusted OR = 2.68, 95% CI = 1.28-5.62, P = 0.009) and rs7975232 CC genotype (Recessive model: adjusted OR = 2.25, 95% CI = 1.10-4.58, P = 0.026). Moreover, rs2239185 and rs7975232 ( P < 0.01) showed significant cumulative effects on OLP risk. .Haplotype analysis showed that the CC haplotype (rs2239185-rs7975232) was associated with an increased risk of OLP (OR =3.11, 95% CI = 1.42-6.83, P = 0.005), compared with the AC haplotype . In conclusion, the rs2239185 and rs7975232 variants of VDR may influence OLP susceptibility, and VDR gene polymorphisms may be candidate susceptibility regions for OLP in a Chinese Han population.

Health Policy

Infectious Diseases

Health Economics & Outcomes Research

Oral lichen planus

Vitamin D receptors

Risk

Single nucleotide polymorphisms

Oral lichen planus (OLP) is a chronic inflammatory disease of the oral mucosa mediated by T cells, whose etiology remains unknown. OLP is characterized as dense lymphocyte infiltration and basal keratinocyte degeneration observable under a microscope [1]. OLP, the typical clinical feature of which include white stripes, can manifest as reticular, papular, plaque-like, erosive, atrophic and bullous [2,3]. Erosive-like lesions are considered to be the most threatening condition and are characterized by pain, ranging from mild discomfort to severe onset [4].The pain seriously affects the patient's eating experience and food digestion, reducing the patient^,s quality of life. .

Previous studies have suggested that vitamin D (VD) deficiency may be associated with an increased risk of some inflammatory diseases, such as OLP and inflammatory bowel disease[5,6]. OLP patients presented a nearly 50% reduction in mucosal VD levels, which may be caused by immunoreactions[6]. As a ligand-induced transcription factor, vitamin D receptors (VDRs) encoded by the VDR gene (chromosomal location 12q12-14) play an important role in regulating the role of vitamin D [7.8]. Increasing evidence suggests that single nucleotide polymorphisms (SNPs) in vitamin D-related genes could affect the properties of vitamin D, such as its anti-carcinogenic effects[9]. Thus, we speculated that VDR gene polymorphisms may be related to OLP. Since OLP is considered as a potential precancerous lesion, specific SNPs in VDR or vitamin D pathway genes may also play an important role in oral cancer.

Based on the above, we conducted this study in a Chinese Han population to investigate the association between key polymorphisms in VDR genes and OLP susceptibility.

Study groups and samples

A total of 177 patients with OLP from the Affiliated Hospital of Stomatology, Nanjing Medical University, Jiangsu Province, China were enrolled in this study between January 2017 and June 2018. . The inclusion criteria for OLP patients were as follows: (1) > 18 years old; (2) diagnosed as OLP by an oral pathologist using a biopsy specimen; and (3) treatment-naïve (the patient did not receive relevant treatment prior to inclusion in the study). Pregnant women, patients with other oral diseases (for example, lichenoid reaction lesions), patients receiving systemic or topical steroids over the past three months, and patients with autoimmune diseases were excluded. The control group included 207 healthy subjects who underwent a physical examination at the physical examination center and had no oral mucosal lesions, inflammation, infection, or autoimmune diseases such as systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). The diagnostic criteria used in this study were diagnostic guidelines developed by van der Meij et al. according to the World Health Organization (WHO) definition of OLP [10].

The oral mucosa of all participants was assessed by two experienced oral medicine specialists. If there was a disagreement between the two examiners, a third clinically experienced oral medicine specialist would make the judgment. The main clinical features, including clinical subtype, affected sites, the number of sites, the presence of cutaneous lesions, and the types of oral lesions and symptoms, were collected for further analyses. All subjects were informed of the purpose of the study and signed the informed consents. Information, such as demographic data, alcohol consumption habits and oral hygiene, were collected by one-to-one surveys using a questionnaire designed according to our research content. Prior to OLP diagnosis, participants who drank more than 20 alcoholic drinks per week were classified as heavy drinkers[11]. The periodontal status of all subjects including the gingival index (GI), periodontal index (PI) and bleeding on probing (BOP) was evaluated in both groups. The oral hygiene of subjects was defined as poor when both GI and PI were≥2, and the BOP was 1. Additionally, 10 ml of venous blood was collected from each subject for biochemical tests and SNP determination.

DNA isolation and genotyping

Genomic DNA was extracted from peripheral blood samples using protease K digestion and phenol/chloroform purification according to a standard protocol. The TaqMan allelic discrimination technology via an ABI 7900HT Sequence Detection system (Applied Biosystems, San Diego, California, USA) was used to explore polymorphisms at the chosen SNPs. Polymerase chain reaction (PCR) was executed with the following thermal profile: 50 twarer 2 min to preheat, 95 °C for 10 min for preincubate, followed by 40 cycles at 95 e with the 50 twarer 2 mito anneal thermal profile. The genotyping results were detected by LightCycler LC480 real-time PCR (Roche Diagnostics, Mannheim, Germany), with a 100% success rate. Two blank controls were specified to a 384-well format for quality control with 10% of the samples randomly selected as repeat samples, producing 100% concordance.

Information regarding VDR SNPs was acquired from the NCBI dbSNP database (http://www.ncbi.nlm.nih.gov/SNP) and the Chinese Han population database in HapMap (http://www.hapmap.org). All SNPs were selected according to the following criteria: (1) minor allele frequency (MAF) ≥0.05 in the Chinese population and (2) a Hardy-Weinberg equilibrium test P-value ≥0.05. Tag SNPs were chosen to represent a set of variants with strong linkage disequilibrium (LD) [11]. A total of eight SNPs in the VDR gene (rs731236, rs739837, rs757343, rs2107301, rs2239185, rs7975232, rs11574129 and rs11568820) were selected according to the above steps.

Statistical analysis

All analyses were performed in Stata/SE (V.12.0 for Windows). Differences in the demographic characteristics between the case and control groups were analyzed by the Student-t test (for continuous variables) or chi-square (χ²) test (for categorical variables). The relationship between a candidate SNP and OLP risk was estimated by multivariate logistic regression analysis, and the results were expressed as odds ratio (ORs) and its 95% confidence interval (CI). The heterogeneity between the corresponding subgroups was examined by the Q test. The Cochran-Armitage test was used for trend analysis. Haplotype analysis was performed to explore the relationship between two significant SNPs and OLP risks. The PHASE software (v2.1) was used to estimate the haplotype frequency based on the observed genotypes. The Single-fold view software (version 4.2) was used to analyze linkage disequilibrium (LD) parameters (i.e., D and r²) [12] and the Thesias software (version 3.1) was used to analyze associations of identified haplotypes in the VDR gene with OLP [13].

Demographic information on 177 OLP patients and 207 healthy subjects is shown in Table 1. There were similar age and gender distributions between the two groups (P=0.155 and 0.091, respectively). However, compared with the control group, OLP patients had more alcohol consumption and better oral hygiene (P <0.05).

The genotype distribution of the eight SNPs in the two groups was described using dominant, recessive and additive genetic models in Table 2. The recessive genetic model computed by logistic regression analyses showed that rs2239185 and rs7975232 were significantly associated with OLP susceptibility. Patients carrying the rs2239185-TT genotype (adjusted OR=2.39, 95%CI=1.10 -5.18, P = 0.027) and rs7975232-CC genotype (adjusted OR=2.65, 95%CI=1.24 -5.66, P = 0.012) tended to have a higher risk of OLP.

The cumulative effects of the two SNPs on OLP were evaluated by the Cochran-Armitage trend test.. The results showed that the risk of OLP increased as the number of mutations increased (Table 3). The OLP risk increased in subjects carrying one or both of the rs2239185 and rs7975232 alleles (OR= 2.33, 95% CI=1.22-4.43). In stratified analyses on the combined variant alleles (rs2239185 and rs7975232) and OLP risk susceptibility, no heterogeneity was observed (Table 4).

LD information for the two SNPs is shown in Table 5. We performed haplotype analysis to assess the effects of the rs2239185 and rs7975232 haplotype variant alleles on the OLP risk (Table 5). When compared with the most frequent AC haplotype, the CC haplotype was significantly associated with OLP susceptibility (OR= 3.11, 95%CI=1.42-6.83), which was consistent with the single SNP analysis.

To further explore the biological significance of rs2239185 and rs7975232 in VDR, we also searched for expression quantitative trait loci (eQTL) evidence based on the public GTEx database (https://gtexportal.org/). We found that the VDR rs2239185 and rs7975232 genotypes were significantly associated with the expression of VDR in whole blood. Mutations associated with VDR rs7975232 and rs2239185 down-regulated of VDR gene expression in whole blood (P = 0.002 and 0.006, respectively, Fig. 1).

Approximately 0.5% to 2.0% of patients with OLP can progress to malignant transformation [14]. Finding new markers that can effectively identify people at a high risk for OLP can help prevent and control OLP and reduce the incidence of malignant transformation. Previous studies have highlighted the role of genetic polymorphisms in susceptibility to OLP [15]. The current study was designed to investigate the effects of genetic variation in the VDR gene and related environmental factors on susceptibility to OLP. The results of this study showed that VDR rs2239185-TT and rs7975232-CC increased the susceptibility to OLP, and that the OLP risk of adult women was higher than that of men, as observed in other studies [16,17].

Vitamin D and its receptors are mainly involved in the regulation of immune regulation and calcium and phosphorus metabolism regulation. A series of evidence suggests that vitamin D deficiency is highly prevalent among the general population in China, which may be related to genetic variation in VDR [18]. Previous studies have shown that VDR genetic variants (such as rs1544410, rs7975232 and rs731236) can cause diseases, such as prostate cancer and hepatocellular carcinoma [19, 20] by affecting the biological effects of vitamin D.Recent studies have linked vitamin D deficiency with immune-related diseases and infectious diseases, e.g., systemic lupus erythematosus and tuberculosis [21]. Bin Zhao et al. found that the VD/VDR signaling pathway can prevent OLP development by mediating the NF-κB pathway [22]. Our study investigated whether genetic variation of VDR affects susceptibility to OLP. And the results revealed that mutations in VDR rs2239185 and rs7975232 increased OLP susceptibility, and cumulative effect analysis showed that OLP risk increased with increasing adverse alleles. The heterogeneity test suggested no interactions between different genotypes in different populations, which confirmed that our final results were robust and unaffected by other factors. Additionally, LD was found between VDR rs7975232 and rs2239185 in our study, which was also observed in previous studies [23, 24,25]. Haplotype analysis showed that SNP-SNP interactions in the VDR gene increased susceptibility to OLP, which further validated the single-gene analysis results. .

It is worth noting that our findings differ from those of Bojan Kujundzic et al., which found that the genetic polymorphism associated with OLP risk was not VDR rs7975232 but VDR rs2228570 (rs2239185 was not included in the study) [11]. Moreover, haplotype analysis between rs7975232 and rs731236 showed that the AT haplotype decreased OLP risk, compared with the most common haplotype CT, further confirming that OLP susceptibility was not caused by a single SNP. The study included only 65 patients with oral lichen planus and 100 healthy blood donors, all of whom were Caucasian and Serbian, which may be the main reason for the differences between the two studies. Many previous studies have shown that the incidence of OLP, clinical symptoms and the mutation rate of VDR genes are different in different races [26, 27]. Nonetheless, the true association between OLP risk and VDR gene variation needs to be further confirmed in larger sample cohort studies and functional experimental studies.

The gene encoding VDR, which is located on chromosome 12q13, consists of 9 exons and 8 introns, and is approximately 75 kb in length [30]. Both rs2239185 and rs7975232 are located in a VDR gene intron, and their polymorphism can affect messenger RNA transcription and protein translation by regulating gene transcription to change the expression and function of VDR [29]. Moreover,the GTEx database showed that VDR expression in the blood was indeed affected by genetic variation associated with rs2239185 and rs7975232. Therefore, we hypothesized that the rs2239185 and rs7975232 variants , as well as the CC haplotypes between the two, may affect VDR expression in whole blood by interfering with transcription. Moreover, the binding of VD to VDR in whole blood and oral keratinocytes was reduced, preventing the activation of the vitamin D/VDR signaling pathway [22]. Thus, functions related to the VDR signaling pathway are inhibited, such as anti-inflammatory effects, eventually leading to the occurrence of OLP.

We acknowledge that there are limitations in this study. Although various analyses were used to reveal the potential impact of VDR gene polymorphisms on OLP susceptibility, the existing epidemiological evidencepresented in this study was not sufficient to speculate on the role of the VDR gene, indicating that our findings require confirmation by functional studies. However, our study also has advantages. First, this is the first study to find genetic evidence that the VDR gene is associated with OLP susceptibility in a Chinese Han population. Second, the sample size of this study is larger than the existing related research [11].

This is the first study to show that genetic mutations in VDR are associated with OLP susceptibility, and that rs2239185 and rs7975232 may be the genetic markers for OLP susceptibility in a Chinese Han population. However, larger scale prospective studies and functional experiments are required to validate our findings.

Acknowledgements

The authors thank Haozhi Fan,Feng Zang,Mei Liu,Lingyun Zhuo and Jingjing Wu for their help

with laboratory work.

Funding

1.Scientific Research Fund of National Health Commission of the People’s Republic of China (201502002)

2.Science and technology development fund project of Nanjing Medical University（2016NJMU056）

Availability of data and materials

The datasets used and analysed during the current study are available from the corresponding author on reasonable request.

Author Contributions：

HS wrote the paper. HS, PH, RY and JY participated in the design of the study. HS, QL and GW carried out the surveys and experiments. HS, FZ and LZ performed the statistical analysis.ML, LZ, JW and HF contributed materials and analysis tools. All authors read and approved the final manuscript.

Ethics approval and consent to participate

This study was approved by the research and ethical committee of Nanjing Medical University, ( ethical review 2017(445),Nanjing, China), and written consent was acquired from the

patients.

Consent for publication

Not applicable.

Competing interests

The authors declare no conflict of interest.

Author details

¹ Department of Pediatric and Preventive dentistry, Affiliated Hospital of Stomatology, Nanjing Medical University, Jiangsu Key Laboratory of Oral Diseases, Nanjing 210029, China

² Department of oral mucosal disease, Affiliated Hospital of Stomatology, Nanjing Medical University, Jiangsu Key Laboratory of Oral Diseases, Nanjing 210029, China

³ Department of Epidemiology and Biostatistics, School of Public Health, Key Laboratory of Infectious Diseases, Nanjing Medical University, Nanjing 211166, China

⁴ Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Jiangsu Key Laboratory of Oral Diseases, Nanjing 210029, China

The information of corresponding authors:

Rongbin Yu:

Tel: 86-25-86869187; FAX: 86-25-86868499; E-mail: [email protected]

Mailing address: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China

Jianrong Yang:

Tel: 86-25-85031971; E-mail: [email protected]

Mailing address: Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology,

Nanjing Medical University, Nanjing 210029, China

Gupta S, Jawanda MK.Oral lichen planus:An update on etiology,pathogenesis,clinical presentation,diagnosis and management.Indian J Dermatol.2015;60(3):222-229.
Van der Meij EH, Schepman KP, van der Waal I.The possible premalignant character of oral lichen planus and oral lichenoid lesions:A prospective study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003;96(2):164–171.
Ismail SB, Kumar SKS, Zain RB.Oral lichen planus and Lichenoid reactions; etiopathogenesis, diagnosis, management and malignant transformation. J Oral Sci. 2007; 49(2):89-106.
Payeras MR, Cherubini K, Figueiredo MA, Salum FG.Oral lichen planus:Focus on etiopathogenesis.Arch Oral Biol.2013;58(9):1057-69.
Du J,Chen Y, Shi Y, Liu T, Cao Y, Tang Y, Ge X, Nie H, Zheng C, Li YC.1,25-Dihydroxyvitamin D Protects Intestinal Epithelial Barrier by Regulating the Myosin Light Chain Kinase Signaling Pathway. Infammatory bowel diseases.2015;21(11):2495–2506
Du J,Li R,Yu FY,Yang F,Wang JH,Chen QY,Wang XY,Zhao B,Zhang F:Experimental study on 1,25(OH)₂D₃ amelioration of oral lichen planus through regulating NF--kB signaling pathway. Oral Dis.2017;23:770–778.
Uitterlinden AG, Fang Y, Van Meurs JB, Pols HA, Van Leeuwen JP.Genetics and biology of vitamin D receptor polymorphisms.Gene.2004; 338(2):143–156.
Whitfield GK, Remus LS, Jurutka PW, Zitzer H, Oza AK, Dang HT, Haussler CA, Galligan MA, Thatcher ML, Encinas Dominguez C, Haussler MR.Functionally relevant polymorphisms in the human nuclear vitamin D receptor gene. Mol Cell Endocrinol.2001; 177(1–2):145–159.
Deeb KK, Trump DL, Johnson CS.Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nat Rev Cancer.2007; 7(9):684-700.
Van der Meij EH, van der Waal I.Lack of clinicopathologic correlation in the diagnosis of oral lichen planus based on the presently available diagnostic criteria and suggestions for modifications.J Oral Pathol Med.2003 32:507-12.
Bojan Kujundzic,Katarina Zeljic,Gordana Supic Marko Magic,Dragan Stanimirovic, Vesna Association of vdr, cyp27b1, cyp24a1 and mthfr gene polymorphisms with oral lichen planus risk.Clin Oral Invest.2016; 20:781-789.
Barrett JC, Fry B, Maller J, Daly MJ.Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics.2005; 21(2):263-265.
Tregouet DA, Garelle V.A new JAVA interface implementation of THESIAS: testing haplotype effects in association studies.Bioinformatics.2007; 23(8):1038–1039.
Fitzpatrick SG,Hirsch SA,GordonSC.The malignant transformation of oral lichen planus and oral lichen oid lesions:a systematic review. J Am Dent Assoc.2014; 145(1):45–
Wang Z, Yao H, Cui B, Ning G, Tang GY.Genetic linkage analysis of oral lichen planus in a Chinese family. Genet Mol Res.2011;10(3):1427-1433.
Georgakopoulou EA, Achtari MD, Achtaris M, Foukas PG,Kotsinas A.Oral lichen planus as a preneoplastic inflammatory model. J Biomed Biotechnol.2012;759626. doi:10.1155/2012/759626.
Baccaglini L, Thongprasom K, Carrozzo M, Bigby M.Urban legends series: lichen Oral Dis.2013; 19(2):128–143.
Abdel-Wareth, L., Haq, A., Turner, A., Khan, S., Salem, A., Mustafa, F., Hussein, N., Pallinalakam, F., Grundy, L., Patras, G., Rajah, J. Total vitamin D assay comparison of the Roche Diagnostics “vitamin D total” electrochemiluminescence protein binding assay with the Chromsystems HPLC method in a population with both D2 and D3 forms of vitamin D. Nutrients.2013;5:971–980.
Salimi, S., Farajian-Mashhadi, F., Alavi-Naini, R., Talebian, G., Narooie-Nejad, M.Association between vitamin D receptor polymorphisms and haplotypes with pulmonary tuberculosis. Biomed Rep. 2015;3:189–194.
Yao, X., Zeng, H., Zhang, G., Zhou, W., Yan, Q., Dai, L., Wang, X. The associated ion between the VDR gene polymorphisms and susceptibility to hepatocellular carcinoma and the clinicopathological features in subjects infected with HBV. Biomed. Res. Int. 2013; 953974.
Carvalho, C., Marinho, A., Leal, B., Bettencourt, A., Boleixa, D., Almeida, I., Farinha, F., Costa, P.P., Vasconcelos, C., Silva, B.M.Association between vitamin D receptor (VDR) gene polymorphisms and systemic lupus erythematosus in Portuguese patients. Lupus. 2015;24:846–853.
Zhao B, Li R, Yang F, et al. LPS-induced vitamin D receptor decrease in oral keratinocytes is associated with oral lichen planus[J]. Scientific reports, 2018, 8: 763.
Jingwi EY, Abbas M, Ricks-Santi L, Winchester D, Beyene D, Day A, Naab TJ, Kassim OO, Dunston GM, Copeland RL Jr, Kanaan YM.Vitamin D receptor genetic polymorphisms are associated with PSA level, Gleason score and prostate cancer risk in African-American men.Anticancer Res. 2015;35(3):1549-1558.
Li W, Guo L, Li H, Sun C, Cui X, Song G, Wang J, Zhang Q.Polymorphism rs2239185 in vitamin D receptor gene is associated with severe community-acquired pneumonia of children in Chinese Han population: a case-control study.Eur J Pediatr. 2015;174(5):621-629.
Alves Pereira Neto T, Costa Pereira AA, Costa Hanemann JA, Coelho LFL, Malaquias LCC.DC-SIGN and VDR polymorphisms are associated with chronic form of paracoccidioidomycosis with oral manifestations.2019; 62(2):186-192.
Papadopoulou A, Kouis P, Middleton N, Kolokotroni O, Karpathios T, Nicolaidou P, Yiallouros PK: Association of vitamin D receptorgene polymorphisms and vitamin D levels with asthma and atopy in Cypriot adolescents: a case-control study. Multidiscip Respir Med. 2015; 10(1): 26.
Thongprasom K, Mravak-Stipetić M, Luckprom P, et al. Oral lichen planus: a retrospective comparative study between Thai and Croatian patients[J]. Acta Dermatovenerologica Croatica, 2009, 17(1): 0-0.
Zmuda JM,Cauley JA,Ferrell RE.Molecular epidemiology of vitamin D receptor gene variants.Epidemiologic Reviews. 2000; 22(2):203-217.
Valdivielso JM, Fernandez, E.Vitamin D receptor polymorphisms and diseases.Clin Chim Acta. 2006;371:1-12.
Mengping Wu , Ming Yue , Peng Huang , Yun Zhang , Chaonan Xie , Rongbin Yu , Jun Li , Jie Wang. Vitamin D level and vitamin D receptor genetic variations contribute to HCV infection susceptibility and chronicity in a Chinese population. Infection, Genetics and Evolution. 2016;41:146–152.

Table 1. Characteristics of clinical data between OLP and control group

Variables	OLP	Control	P-value
	(n = 177)	(n = 207)
Mean age, year	49.20 ± 14.14	48.47 ± 10.88	0.569
< 45	61(34.46)	86(41.55)	0.155
≥ 45	116(65.54)	121(58.45)
Gender
Male (%)	49(27.68)	74(35.75)	0.091
Female (%)	128(72.32)	133(64.25)
Alcohol
Heavy	11(6.21)	2(0.97)	0.005
Non Heavy	166(93.79)	205(99.03)
Oral hygiene
Good	131(74.01)	119(57.49)	0.001
Poor	46(25.99)	88(42.51)

Abbreviation: OLP, oral lichen planus.

Table 2. Distribution of VDR genotypes between OLP and control group

Genotype	OLP	Control	OR (95% CI)	P-value
rs731236
CC	154(87.01)	180(86.96)	1.00	--
CT	21(11.86)	24(11.59)	0.99(0.51-1.91)	0.979
TT	2(1.13)	3(1.45)	0.93(0.15-6.06)	0.946
Dominant			0.99(0.52-1.85)	0.965
Recessive			0.94(0.15-6.05)	0.947
Additive			0.98(0.57-1.71)	0.954
rs739837
CC	98(55.37 )	112(54.11)	1.00	--
CA	61(34.46)	82(39.61 )	0.73(0.45-1.20)	0.218
AA	18(10.17)	13(6.28)	1.36(0.60-3.09)	0.468
Dominant			0.82(0.51-1.31)	0.404
Recessive			1.60(0.73-3.50)	0.242
Additive			0.98(0.69-1.41)	0.927
rs757343
AA	113(63.84)	128(61.84 )	1.00	--
AG	53(29.94)	73(35.27)	0.70(0.43-1.15)	0.163
GG	11(6.21)	6(2.9 )	2.06(0.70-6.13)	0.180
Dominant			0.81( 0.50-1.29)	0.375
Recessive			2.36(0.81-6.89)	0.117
Additive			0.97(0.66-1.44)	0.893
rs2107301
CC	83(46.89)	96(46.38)	1.00	--
CT	79(44.63)	93(44.93)	1.03(0.67-1.60)	0.883
TT	15 (8.47)	18 (8.7)	1.19(0.54-2.58)	0.668
Dominant			1.06(0.69-1.61)	0.800
Recessive			1.17(0.55-2.45)	0.686
Additive			1.07(0.77-1.48)	0.706
rs2239185
CC	90 (50.85)	111(53.62)	1.00	--
CT	62(35.03)	83 (40.10)	0.78(0.47-1.27)	0.315
TT	25(14.12)	13 (6.28)	2.39(1.10-5.18)	0.027
Dominant			1.00(0.63-1.59)	0.995
Recessive			2.68(1.28-5.62)	0.009
Additive			1.24(0.88-1.74)	0.206
rs7975232
AA	81(45.76)	118(57.00)	1.00	--
AC	70(39.55)	74(35.75)	1.36(0.83-2.23)	0.225
CC	26(14.69)	15(7.25)	2.65(1.24-5.66)	0.012
Dominant			1.57(0.97-2.50)	0.061
Recessive			2.25(1.10-4.58)	0.026
Additive			1.54(1.09-2.18)	0.014
rs11574129
CC	119(67.23)	146(70.53)	1.00	--
CT	50(28.25)	57(27.54)	0.97(0.59-1.61)	0.921
TT	8(4.52)	4(1.93)	2.49(0.70-8.84)	0.159
Dominant			1.08(0.67-1.75)	0.740
Recessive			2.50(0.71-8.84)	0.154
Additive			1.17(0.78-1.76)	0.439
rs11568820
AA	61(34.46)	74(35.75)	1.00	--
AG	81(45.76)	96(46.38)	1.10(0.69-1.76)	0.695
GG	35(19.77)	37(17.87)	1.26(0.69-2.28)	0.454
Dominant			1.14(0.74-1.78)	0.551
Recessive			1.19(0.70-2.03)	0.520
Additive			1.12(0.83-1.50)	0.455

Logistic regression analyses adjusted for age, gender, alcohol, oral hygiene.

Abbreviation:VDR,vitamin D receptor ;OLP, oral lichen planus; OR, odds ratio; CI, confident interval.

Table 3. Cumulative Effects of rs2239185 and rs7975232 on OLP risk

Variables	OLP n(%)	Control n(%)	OR(95%CI)	P-value
0	145 (81.92)	188 (90.82)	1.00	-
1	13 (7.34)	10 (4.83)	1.82 (0.74-4.48)	0.190
2	19 (10.73)	9 (4.35)	2.87 (1.21-6.81)	0.017*
Trend				P a=0.007
0	145 (81.92)	188 (90.82)	1.00	-
1-2	32 (18.08)	19 (9.18)	2.33 (1.22-4.43)	0.010

Variables are numbers of combined unfavorable alleles (rs2239185-TT and rs7975232-CC).

Logistic regression analyses adjusted for age, gender, alcohol consumption and oral hygiene. Pa-value was analyzed by Cochran-Armitage trend test.

Abbreviation: OLP, oral lichen planus; OR, odds ratio; CI, confident interval.

Table 4. Stratified analyses on combined variant alleles (rs2239185 and rs7975232) and OLP risk

Variables	OLP risk (0 vs.1-2)		OR (95%CI)	P a	P b
	OLP	Control
Age, year
≥ 45	50/11	75/11	1.69 (0.60-4.71)	0.318	0.457
< 45	95/21	133/8	3.13 (1.28-7.65)	0.012
Gender
Male	40/9	58/16	0.61 (0.21-1.72)	0.347	0.267
Female	105/23	130/3	10.11 (2.82-36.30)	<0.001
Alcohol
Heavy	8/3	1/1	--	--	--
Non Heavy	137/29	187/18	2.42 (1.25-4.67)	0.008
Oral hygiene
Good	109/22	103/16	1.59 (0.75-3.37)	0.231	0.453
Poor	36/10	85/3	6.47 (1.56-26.90)	0.010

Logistic regression was used in the implicit model to determine the adjusted P a value according to age, gender, alcohol consumption and oral hygiene, heterogeneity was used to test

P b-value.

Abbreviation: OLP, oral lichen planus; OR, odds ratio; CI, confident interval.

Table 5. Haplotypes analysis of rs2239185 and rs7975232 with OLP risk

Haplotype	OLP n(%)	Control n(%)	OR	P
AC	218 (61.59)	295 (71.26)	1.00	1.00
CT	98 (27.68)	94 (22.70)	1.38 (0.96-1.97)	0.084
CC	24 (6.78)	10 (2.42)	3.11 (1.42-6.83)	0.005
AT	14 (3.95)	15 (3.62)	1.21 (0.55-2.66)	0.633

Logistic regression analyses adjusted for age, gender,alcohol consumption and oral hygiene

SNPs order: rs2239185 and rs797523

Download PDF

Journal Publication

published 30 Jan, 2020

Read the published version in BMC Oral Health →

Editorial decision: Minor revision
15 Oct, 2019
Review #1 received at journal
09 Sep, 2019
Review #2 received at journal
25 Aug, 2019
Reviewer #2 agreed at journal
24 Aug, 2019
Reviewers invited by journal
21 Aug, 2019
Reviewer #1 agreed at journal
21 Aug, 2019
Editor assigned by journal
20 Aug, 2019
Submission checks completed at journal
19 Aug, 2019
Editor invited by journal
19 Aug, 2019

You are reading this older preprint version

Read the latest preprint version →

Vitamin D receptor genetic polymorphisms are associated with oral lichen planus susceptibility in a Chinese Han population

Status:

Journal Publication

Version 2

Abstract

Figures

Background

Material and methods

Results

Discussion

Conclusion

Declarations

References

Tables

Status:

Journal Publication

Version 2