| Abstract |
SUMMARY
Background. Diabetes mellitus type 1 (T1D) is a common immune-mediated multifactorial disease, on which recent epidemiological data suggest a strong genetic susceptibility. Recent interesting knowledge is the association between the genetic susceptibility to type 1 diabetes and vitamin D Receptor polymorphisms. Four polymorphisms in the VDR gene have been extensively studied: i.e., FokI F>f (rs10735810), BsmI B>b (rs1544410), ApaI A>a (rs7975232), and TaqI T>t (rs731236). Staphylococcus aureus is a major pathogen for humans with increasing resistance to antibiotics. The anterior nares are the primary ecological reservoir of S. aureus, and nasal carriage has been related to progress to staphylococcal disease. Periodontal disease is one of the most prevalent infectious diseases worldwide, affecting up to 90% of the population and up to 50% of school-aged children. Periodontal disease is generally considered to be more prevalent in individuals with type 1 diabetes (T1D).
Objectives. In this study we tried to assess the contribution of VDR polymorphisms to the susceptibility to T1D in the population of Crete. We also investigated whether the four most commonly studied polymorphisms in the VDR gene are associated with colonization by and persistent carriage of S. aureus in individuals with T1D. Finally we tried to investigate the potential risk factors of gingivitis in our population.
Population and methods. The study group consisted of a cohort of 170 T1D patients, followed up at the outpatient diabetic clinic of the Department of Pediatrics, University Hospital of Heraklion, Crete, Greece. The control group consisted of 96 unrelated children-residents of Crete with no history of autoimmune or other chronic diseases. Whole blood was collected and genomic DNA was isolated from blood leucocytes by using the kit Puregene, Gentra, and amplified with standard PCR
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techniques. Nasal specimens were obtained by rotating a sterile fiber-tipped swab four times in both anterior nares of each enrolled individual. A second nasal swab culture was obtained after a minimum interval of 3 months. Gingivitis was defined by the presence of easily bleeding with brushing or flossing and the presence of gingival redness, swelling and loss of contour.
Results. Distribution of VDR genotype and allele frequencies differed significantly between patients with T1D and controls in all four genotypes. FokI FF genotype and F allele, and BsmI BB genotype and B allele were less frequent in individuals with T1D. On the other hand, ApaI AA genotype and A allele, as well as TaqI TT genotype and T allele were more frequent in individuals with T1D.
Regarding to the association between VDR polymorphisms and S. aureus nasal carriage, S. aureus nasal colonization was more common in individuals with TaqI T than t allele, and TaqI TT homozygotes were more colonized by S. aureus than genotypes TaqI tt and Tt combined. Furthermore, ApaI AA homozygotes were less colonized than ApaI aa and Aa genotypes combined. No significant differences were observed for BsmI and FokI genotypes. S. aureus persistent nasal colonization was more common in individuals with TaqI T than t allele (29,3% vs. 17,0%), although at a marginally significant level. Furthermore TaqI TT homozygotes were persistently colonized by S. aureus more than genotypes TaqI tt and Tt combined. ApaI AA homozygotes were less persistent carriers than ApaI aa and Aa genotypes combined.
Gingivitis was present in 52/112 (46%) patients and gingivitis frequency was associated with the duration of diabetes, and with age. Furthermore, individuals with gingivitis were more often colonized by S. aureus.
Discussion. Our findings point to relationship between VDR polymorphisms FokI, BsmI, ApaI, and TaqI and susceptibility to T1D in a Mediterranean island with one of 12
the lowest T1D incidence rates in Europe. Our findings also suggest that two VDR polymorphisms, TaqI and ApaI, are related to colonization by and persistent nasal carriage of S. aureus in individuals with T1D. Our study failed to confirm association between gingivitis and glycaemic control in individuals with type 1 diabetes. Another finding, which has not been reported up to date, is the significant relationship between gingivitis and nasal colonisation of S. aureus. Finally, previous observations suggest that the VDR gene TaqI polymorphism is a useful risk marker for periodontitis, a finding which was not confirmed in our study..
Our cohort was not large enough, and the results need to be confirmed in larger studies. Hence, as we managed to enroll the majority of patients with T1D on the island of Crete, our study provides the benefits of a well-defined area, and of a population with one of the lowest T1D prevalence in Europe. Our findings suggest that genetic variation in the vitamin D receptor gene affects nasal colonization by S. aureus in individuals with type 1 diabetes, and further contribute to the understanding of the immunoregulatory role of vitamin D in the host’s response and susceptibility to infection. Further work is required to explore genetic and environmental factors that potentially enhance or inhibit this role of VDR polymorphisms in T1D, such as the contribution of ultraviolet radiation exposure and other environmental determinants of vitamin D status.
Finally, we did not prove any significant difference in the frequency of the infections we investigated between S. aureus colonized and non-colonized patients.
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Πολυμορφισμοί του υποδοχέα της βιταμίνης D και ευπάθεια στις λοιμώξεις παιδιών και εφήβων με διαβήτη τύπου 1
