Association between Carbonic Anhydrase VI Gene Copy Number Variations and Dental Caries Experience.

The current study examined the association between the carbonic anhydrase VI (CA VI) copy number variations (CNVs) and dental caries experience in adults. In total, 202 of 35-72 years old subjects participating in the Lithuanian National Oral Health Survey (LNOHS) agreed to provide saliva samples; thus, their data were included in the current study. Information about sociodemographic, environmental, and behavioural determinants was acquired via the self-administered World Health Organization (WHO) questionnaire. Fluoride levels in the drinking water were recorded based on information provided by water suppliers. Dental caries experience was recorded by one calibrated examiner using the WHO criteria for recording caries on smooth (including proximal, buccal, and oral) or occlusal surfaces. Caries experience was measured as the total number of decayed (D3), missing (M), filled (F) surfaces. DNA was extracted from saliva samples to examine CA VI CNVs using the QX200 Droplet Digital PCR system. Negative binomial regression and Poisson regression analyses were employed for data analyses. Based on multivariable regression analyses, higher copy number of CA VI were associated with higher caries experience on smooth surfaces (IRR 1.04, 95% CI: 1.005-1.08) and occlusal surfaces (IRR 1.02, 95% CI: 1.003-1.04). Positive associations between higher copy number of CA VI and higher caries experience on smooth and occlusal surfaces were found, suggesting that the CA VI coding gene may be associated with caries development. Future studies are needed to validate our results and to examine the underlying mechanisms of such associations.

Amylase Alpha 1 Gene (AMY1) Copy Number Variation and Dental Caries Experience: A Pilot Study among Adults in Lithuania.

INTRODUCTION: Genetic biomarkers have the potential to be used in personalised dentistry for improved prevention and decision-making in caries management. The amylase alpha 1 gene (AMY1) encodes salivary α-amylase and may be one such biomarker. We examined the association between AMY1 copy number variation (CNV) and dental caries experience in adults. MATERIALS AND METHODS: A stratified random sample of 193 participants from the Lithuanian National Oral Health Survey (LNOHS) agreed to provide saliva samples and were included in this analysis (age 35-44 years; participation rate 43%). Information on socio-demographic and behavioural characteristics was taken from the LNHOS, which used the self-administered World Health Organisation (WHO) questionnaire. Data on fluoride levels in drinking water at the recruitment areas was recorded based on information provided by water suppliers. Dental caries experience was recorded at a surface level (smooth-surface and occlusal-surface decayed, missing, filled surfaces [D3MFS] score) by one trained and calibrated examiner using WHO criteria, and subsequently dichotomised for the statistical analyses. DNA extracted from saliva samples was used to investigate AMY1 CNV using the QX200 droplet digital PCR system. Bivariate and multivariable statistical analyses were employed. RESULTS: When compared to participants with an AMY1 copy number (CN) of 2-3, higher odds of smooth-surface D3MFS >14 was observed for participants with a CN of 4-5 (OR 13.3, 95% CI 2.1-86.3), 6-9 (OR 7.0, 95% CI 1.4-34.1), and 10-16 (OR 5.8, 95% CI 1.2-32.2). Female sex was independently associated with a smooth-surface D3MFS >14 (OR 5.7, 95% CI 1.9-17.2). CONCLUSIONS: Our study demonstrated an association between AMY1 CNV and high smooth-surface caries experience. Studies with larger sample sizes are needed to validate this association.

Pure anti-dsDNA mAbs need chromatin structures to promote glomerular mesangial deposits in BALB/c mice.

The glomerular targets for nephritogenic antibodies have been identified as membrane-associated chromatin fragments. The processes responsible for their deposition are poorly understood. To determine early events in antibody-mediated nephritis, we injected highly pure anti-dsDNA mAbs into BALB/c mice. Mice receiving one dose of anti-dsDNA mAbs were sacrificed 6 or 24 h later. No direct binding of mAbs to glomerular membranes or to the mesangial matrix was observed by immune electron microscopy. In contrast, repeated injections of the same antibodies over 4 weeks resulted in deposition of electron dense structures predominantly in the mesangial matrix. These structures contained mAbs and chromatin fragments as determined by co-localization immune electron microscopy. Biotinylated anti-dsDNA mAbs, injected into nephritic (NZB x NZW)F1 or MRL(lpr/lpr) mice were detected in newly formed electron dense structures within glomerular capillary membranes. There were no correlation between mAb affinity for DNA, as determined by surface plasmon resonance analyses, and ability to bind chromatin fragments in vivo. No direct binding of mAbs to inherent membrane antigens was observed. Quantification of DNA in sera before and after one single injection of antibodies revealed increased DNA levels at 6 h after injection of anti-dsDNA mAb, and lower levels after 24 h. Repeated injections of anti-dsDNA caused an increase in circulating DNA. These results indicate that availability of chromatin fragments, presumable in circulation, is important for glomerular mesangial matrix deposition of anti-dsDNA antibody-containing immune complexes in context of lupus nephritis.