A causal association between asthma and dental caries: a two-sample bidirectional Mendelian randomization study

Background: Dental caries and asthma are two of the most prevalent chronic illnesses among children. Previous research has indicated a correlation between the two, but confounding factors and inverted causality may influence this correlation. We conducted a two-sample bidirectional Mendelian randomization analysis to investigate the causal relationship between asthma and dental caries at the genetic level. Methods: We obtained Genome-wide association study (GWAS) summary statistics for asthma from the UK Biobank database, which involved 56,167 cases and 352,255 controls. GWAS datasets of dental caries were obtained from the FinnGen consortium which included 4170 cases and 195,395 controls. We performed a bidirectional Mendelian randomization analysis using the inverse variance weighted (IVW) approach as the primary method. The reliability of the results was verified by heterogeneity, pleiotropy and sensitivity analysis. Results: The results showed that asthma increased the likelihood of developing dental caries (IVW odds ratio (OR) = 1.13, 95% confidence intervals (CI) = 1.03–1.24, p = 0.010), but there was no evidence to suggest that dental caries increased the incidence of asthma (IVW OR = 1.02, 95% CI = 0.97–1.08, p = 0.400). The sensitivity analysis confirmed the validity of these MR results. Conclusions: This study found that asthma increases the likelihood of developing dental caries, but there is no evidence that dental caries is linked to an increased risk of asthma. These findings suggest that more investigations are required to explore possible mediating pathways between the two conditions and that screening and prevention of dental caries in asthmatics should be strengthened in clinical practice.

Mendelian randomization analysis; Dental caries; Asthma

[1] Faustova MO, Ananieva MM, Basarab YO, Dobrobolska OV, Vovk IM, Loban GA. Bacterial factors of cariogenicity (literature review). Wiadomości Lekarskie. 2018; 71: 378–382.

[2] GBD 2019 Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. The Lancet. 2020; 396: 1204–1222.

[3] World Health Organization. Global oral health status report: towards universal health coverage for oral health by 2030. 2022. Available at: https://www.who.int/publications/i/item/9789240061484 (Accessed: 09 January 2024).

[4] Leung JS. Paediatrics: how to manage acute asthma exacerbations. Drugs in Context. 2021; 10: 2020-12-7.

[5] Asher MI, García-Marcos L, Pearce NE, Strachan DP. Trends in worldwide asthma prevalence. European Respiratory Journal. 2020; 56: 2002094.

[6] Johnson CC, Havstad SL, Ownby DR, Joseph CLM, Sitarik AR, Biagini Myers J, et al. Pediatric asthma incidence rates in the United States from 1980 to 2017. Journal of Allergy and Clinical Immunology. 2021; 148: 1270–1280.

[7] Bansala V, Reddy KVG, Shrivastava S, Dhaded S, Noorani SM, Shaikh MI. Oral health assessment in children aging 8–15 years with bronchial asthma using inhalation medication. Tzu Chi Medical Journal. 2022; 34: 239–244.

[8] Tyagi R, Kumar S, Kalra N, Faridi MA, Khatri A, Satish VV. Evaluation of oral health of 6 to 10-year-old asthmatic children receiving bronchodilator through inhaler. Indian Journal of Dental Research. 2019; 30: 670.

[9] Wu FY, Liu JF. Asthma medication increases dental caries among children in Taiwan: an analysis using the national health insurance research database. Journal of Dental Sciences. 2019; 14: 413–418.

[10] Flexeder C, Kabary Hassan L, Standl M, Schulz H, Kühnisch J. Is there an association between asthma and dental caries and molar incisor hypomineralisation? Caries Research. 2020; 54: 87–95.

[11] Rezende G, dos Santos NML, Stein C, Hilgert JB, Faustino‐Silva DD. Asthma and oral changes in children: associated factors in a community of southern Brazil. International Journal of Paediatric Dentistry. 2019; 29: 456–463.

[12] Ho SW, Lue KH, Ku MS. Allergic rhinitis, rather than asthma, might be associated with dental caries, periodontitis, and other oral diseases in adults. PeerJ. 2019; 7: e7643.

[13] Boorsma EM, Rienstra M, van Veldhuisen DJ, van der Meer P. Residual confounding in observational studies: new data from the old DIG trial. European Heart Journal. 2019; 40: 3342–3344.

[14] Bowden J, Holmes MV. Meta-analysis and Mendelian randomization: a review. Research Synthesis Methods. 2019; 10: 486–496.

[15] Birney E. Mendelian randomization. Cold Spring Harbor Perspectives in Medicine. 2022; 12: a041302.

[16] Minelli C. An integrated approach to the meta-analysis of genetic association studies using Mendelian randomization. American Journal of Epidemiology. 2004; 160: 445–452.

[17] Tobin MD. Commentary: development of Mendelian randomization: from hypothesis test to “Mendelian deconfounding” International Journal of Epidemiology. 2004; 33: 26–29.

[18] Lawlor DA. Commentary: two-sample Mendelian randomization: opportunities and challenges. International Journal of Epidemiology. 2016; 45: 908–915.

[19] Skrivankova VW, Richmond RC, Woolf BAR, Yarmolinsky J, Davies NM, Swanson SA, et al. Strengthening the reporting of observational studies in epidemiology using Mendelian randomization. JAMA. 2021; 326: 1614.

[20] Smith GD, Ebrahim S. What can mendelian randomisation tell us about modifiable behavioural and environmental exposures? The BMJ. 2005; 330: 1076–1079.

[21] Davies NM, Holmes MV, Davey Smith G. Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. The BMJ. 2018; 362: k601.

[22] Wang F, Liu D, Zhuang Y, Feng B, Lu W, Yang J, et al. Mendelian randomization analysis identified genes potentially pleiotropically associated with periodontitis. Saudi Journal of Biological Sciences. 2021; 28: 4089–4095.

[23] Burgess S, Thompson SG. Avoiding bias from weak instruments in Mendelian randomization studies. International Journal of Epidemiology. 2011; 40: 755–764.

[24] Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. International Journal of Epidemiology. 2015; 44: 512–525.

[25] Verbanck M, Chen C, Neale B, Do R. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nature Genetics. 2018; 50: 693–698.

[26] Nolte IM. Metasubtract: an R-package to analytically produce leave-one-out meta-analysis GWAS summary statistics. Bioinformatics. 2020; 36: 4521–4522.

[27] Agostini BA, Collares KF, Costa FDS, Correa MB, Demarco FF. The role of asthma in caries occurrence—meta-analysis and meta-regression. Journal of Asthma. 2019; 56: 841–852.

[28] Shah PD, Badner VM, Rastogi D, Moss KL. Association between asthma and dental caries in us (United States) adult population. Journal of Asthma. 2021; 58: 1329–1336.

[29] Moreira LV, Galvao EL, Mourao PS, Ramos-Jorge ML, Fernandes IB. Association between asthma and oral conditions in children and adolescents: a systematic review with meta-analysis. Clinical Oral Investigations. 2023; 27: 45–67.

[30] Fathima R, Shenoy R, Jodalli PS, Sonde L, Mohammed IP. Evaluation of salivary parameters and oral health status among asthmatic and nonasthmatic adult patients visiting a tertiary care hospital. Cureus. 2019; 11: e5957.

[31] Bairappan S, Puranik MP, R SK. Impact of asthma and its medication on salivary characteristics and oral health in adolescents: a cross‐sectional comparative study. Special Care in Dentistry. 2020; 40: 227–237.

[32] Hatipoğlu Ö, Pertek Hatipoğlu F. Association between asthma and caries-related salivary factors: a meta-analysis. Journal of Asthma. 2022; 59: 38–53.

[33] D’Agostino C, Elkashty OA, Chivasso C, Perret J, Tran SD, Delporte C. Insight into salivary gland aquaporins. Cells. 2020; 9: 1547.

[34] Park C, Stafford C, Lockette W. Exercise-induced asthma may be associated with diminished sweat secretion rates in humans. Chest. 2008; 134: 552–558.

[35] Arafa A, AlDahlawi S, Hussien A. Impact of secretory immunoglobulin a level on dental caries experience in asthmatic children. International Journal of Clinical Pediatric Dentistry. 2019; 12: 414–418.

[36] Widhianingsih D, Koontongkaew S. Enhancement of cariogenic virulence properties of dental plaque in asthmatics. Journal of Asthma. 2021; 58: 1051–1057.

[37] Brigic A, Kobaslija S, Zukanovic A. Antiasthmatic inhaled medications as favoring factors for increased concentration of streptococcus mutans. Materia Socio Medica. 2015; 27: 237.

[38] Cherkasov SV, Popova LY, Vivtanenko TV, Demina RR, Khlopko YA, Balkin AS, et al. Oral microbiomes in children with asthma and dental caries. Oral Diseases. 2019; 25: 898–910.

[39] Thomas M, Parolia A, Kundabala M, Vikram M. Asthma and oral health: a review. Australian Dental Journal. 2010; 55: 128–133.

[40] Okabayashi K, Wakao Y, Narita T. Release of secretory immunoglobulin a by submandibular gland via β adrenergic receptor stimulation. Archives of Oral Biology. 2021; 129: 105209.

[41] Sorino C, Negri S, Spanevello A, Visca D, Scichilone N. Inhalation therapy devices for the treatment of obstructive lung diseases: the history of inhalers towards the ideal inhaler. European Journal of Internal Medicine. 2020; 75: 15–18.

[42] Sullivan A, Hunt E, MacSharry J, Murphy DM. The microbiome and the pathophysiology of asthma. Respiratory Research. 2016; 17: 163.

[43] Samec T, Amaechi BT, Jan J. Influence of childhood asthma on dental caries: a longitudinal study. Clinical and Experimental Dental Research. 2021; 7: 957–967.

[44] Baghani E, Ouanounou A. The dental management of the asthmatic patients. Special Care in Dentistry. 2021; 41: 309–318.