Зв'язок BsmI-поліморфізму гена VDR із розвитком хронічного генералізованого пародонтиту

Abstract

Наведено результати вивчення BsmI-поліморфізму гена VDR у 116 хворих iз хронічним генералізованим пародонтитом (ХГП) та 67 осіб контрольної групи. Встановлено, що BsmI-поліморфний варіант гена VDR асоційований із розвитком ХГП в українській популяції. У гомозигот за мінорним алелем (B/B) ризик розвитку ХГП більший, ніж у гомозигот за основним алелем (b/b). Чоловіча стать та надмірна вага підвищують ймовірність настання ХГП у носіїв мінорного В-алеля за поліморфним сайтом BsmI гена VDR.

Представлены результаты изучения BsmI-полиморфизма гена VDR у 116 пациентов с хроническим генерализованным пародонтитом (ХГП) и 67 лиц контрольной группы. Установлено, что BsmIполиморфный вариант гена VDR ассоциирован с развитием ХГП в украинской популяции. У гомозигот по минорному аллелю (B/B) риск развития ХГП больше, чем у гомозигот по основному аллелю (b/b). Мужской пол и избыточный вес повышают вероятность развития ХГП у носите

Introduction. To date, there is growing evidence about the role of endocrine disorders in the development of periodontal pathologies. The active form of vitamin D, 1,25-dihydroxycholecalciferol (1,25-(OH)2D3), is actively studied in this context. In addition to the leading role of this hormone in homeostasis of calcium and mineral metabolism in bone tissue, its important role in the processes of cell differentiation, cell growth and immunological reactions has been proved. The results of recent studies have shown the association between the density of alveolar bone tissue, osteoporosis and loss of teeth. The biological effects of 1,25-(OH)2D3 are realized through its interaction with the nuclear receptor VDR, which regulates the transcription of more than 500 genes in the cells of human body. The association between VDR gene polymorphisms and osteoporosis, renal osteodystrophy, diabetes mellitus type 2, psoriasis, multiple sclerosis, cardiovascular diseases, tumors of various localizations, and periodontal diseases development has been proved in many studies. The study was a part of scientific project “The role of single nucleotide polymorphisms in development of pathological processes and diseases”, supported by the Ministry of Education and Science of Ukraine, № 0114U006297. Purpose. To test the association between VDR gene BsmI polymorphism and сhronic generalized periodontitis development (CGP). Materials and Methods. The buccal epithelial cells of 116 patients with CGP and 67 control subjects were used. VDR gene BsmI (rs1544410) polymorphism genotyping was performed using PCR-RFLP (polymerase chain reaction with following restriction fragment length polymorphism analysis) method. Statistical analyses were performed using Statistical Package for Social Science software (SPSS, version 17.0, Chicago, IL, USA). An odds ratio (OR) and 95% confidence interval (CI) were obtained from logistic regression for dominant, recessive, superdominant and additive models of inheritance. Multivariable logistic regression was used to exclude the effect of other factors including sex, age, body mass index (BMI), diabetes mellitus type 2 (DMT2), arterial hypertension (AH) and smoking status. All statistical tests were twosided, the value of P < 0.05 was considered as significant. Results. Obtained genotype frequencies for BsmI polymorphism did not significantly deviate from Hardy-Weinberg equilibrium expectations both in case and control groups (P > 0.05). However the frequency of VDR BsmI genotypes in CGP patients significantly differed from the control individuals in full cohort (P = 0.046), in male (P = 0.014), nonsmokers (P = 0.040) and subjects with elevated BMI (P = 0.008). After adjustment for covariates of sex, age, BMI, DMT2, AH and smoking status significant genotypic association between VDR gene BsmI locus and CGP was revealed under dominant (Padj = 0.040; ORadj = 1.960, 95 % CI =1.033–3.718) and additive (Padj = 0.023; ORadj = 3.129, 95 % CI =1.168–8.385 – for B/B genotype) models of inheritance. Logistic regression analysis in female subgroup did not show any significant link with CGP development neither before nor after adjustment for covariates (P > 0.05). At the same time in male subjects significant association between VDR BsmI polymorphism and CGP was revealed under dominant (Padj = 0.020; ORadj = 3.172, 95 % CI =1.195–8.420), recessive (Padj = 0.042; ORadj = 9.153, 95 % CI =1.087–77.046), and additive (Padj = 0.022; ORadj = 12.626, 95 % CI = 1.446–110.249 – for B/B genotype) models. Conclusion. VDR gene BsmI polymorphism is associated with chronic generalized periodontitis development in the Ukrainian population. The risk of mentioned disease in B/B genotype carries is higher compared to b/b homozygotes. Male gender and overweight increase the likelihood of the chronic generalized periodontitis occurring in BsmI minor B allele carriers.