Role of Genetic Polymorphisms in Salivary Amylase and Their Impact on Carbohydrate Metabolism and Dental Caries Risks: A Systematic Review and Meta-Analysis
DOI:
https://doi.org/10.36283/ziun-pjmd14-3/069Keywords:
Amylases, Gene Copy Number Variation, Carbohydrate Metabolism , Dental Caries, Metabolic SyndromeAbstract
Background: Salivary amylase demonstrates an important role in carbohydrate metabolism and oral health and is influenced by the amylase alpha-1 gene (AMY1) gene polymorphisms. Amylase activity changes impact starch digestion, microbial interactions, and susceptibility to dental caries. This study aimed to investigate the impact of AMY1 copy number variations (CNV) on carbohydrate metabolism and susceptibility to dental caries.
Methods: This systematic review and meta-analysis were conducted using the PRISMA 2020 guidelines. Up to May 2025, literature was retrieved in PubMed, Scopus, Web of Science, and Google Scholar. The eligible studies tested the relationship between AMY1 CNV or the salivary alpha-amylase and outcome in carbohydrate metabolism or dental caries. Information was independently obtained and then sifted. NOS and JBI were used in measuring the risk of bias. Meta-analyses were done based on odds ratios pooled according to a random-effects model; the outcomes of each single study are described narratively. I2 was taken as the measure of heterogeneity.
Results: A total of nine studies were eligible, five of them being observational studies and four, cross-sectional, with the number of participants totaling 23,938. Two studies on meta-analysis exhibited a strong effect between AMY1 variation and elevated metabolic risk (OR = 1.20; 95% CI: 1.14, 1.26; I2 = 0%). Regarding dental results, there was no significant association between it and high heterogeneity (OR = 3.00, 95% CI: 0, 23 39.97 I2 = 87%). The risk of bias was low to moderate, and the GRADE certainty was moderate to low.
Discussion: The relationship between AMY1 CNV and sAA activity shows promise for their development as individualized healthcare biomarkers between metabolic and oral health factors. However, the limited number of high-quality studies and variability in study designs may affect the generalizability of these findings. Additional research needs to be conducted to improve genetic screening procedures and clinical usage.
References
1. des Gachons CP, Breslin PAS. Salivary Amylase: Digestion and Metabolic Syndrome. Curr Diab Rep. 2016 Oct;16(10):102. doi:10.1007/s11892-016-0794-7
2. Bhattarai KR, Junjappa R, Handigund M, Kim HR, Chae HJ. The imprint of salivary secretion in autoimmune disorders and related pathological conditions. Autoimmun Rev. 2018 Apr;17(4):376-390. doi:10.1016/j.autrev.2017.11.031
3. Mandel AL, Peyrot des Gachons C, Plank KL, Alarcon S, Breslin PAS. Individual differences in AMY1 gene copy number, salivary α-amylase levels, and the perception of oral starch. PLoS One. 2010 Oct;5(10):e13352. doi:10.1371/journal.pone.0013352
4. Superdock DK, Johnson LM, Ren J, Khan A, Eno M, Man S, et al. The Impact of Human Salivary Amylase Gene Copy Number and Starch on Oral Biofilms. Microorganisms. 2025 Feb;13(2):461. doi:10.3390/microorganisms13020461
5. Pajic P, Pavlidis P, Dean K, Neznanova L, Romano RA, Garneau D, et al. Independent amylase gene copy number bursts correlate with dietary preferences in mammals. eLife. 2019;8:e44628. doi:10.7554/eLife.44628
6. Gomez A, Espinoza JL, Harkins DM, Leong P, Saffery R, Bockmann M, et al. Host Genetic control of the oral microbiome in Health and Disease. Cell Host Microbe. 2017 Sep;22(3):269-278. doi:10.1016/j.chom.2017.08.013
7. Pérez-Ros P, Navarro-Flores E, Julián-Rochina I, Martínez-Arnau FM, Cauli O. Changes in Salivary Amylase and Glucose in Diabetes: A Scoping Review. Diagnostics. 2021 Mar;11(3):453. doi:10.3390/diagnostics11030453
8. Erta G, Gersone G, Jurka A, Tretjakovs P. The Link between Salivary Amylase Activity, Overweight, and Glucose Homeostasis. Int J Mol Sci. 2024 Jan;25(18):9956. doi:10.3390/ijms25189956
9. Savitha Priyadarsini S, Naveen Kumar PG, Khairnar MR, Akram Z, Ghodela R, Jadhav SK, et al. Salivary alpha amylase as a diagnostic biomarker for dental caries – A systematic review and meta analysis. Arch Oral Biol. 2025 Feb;170:106136. doi:10.1016/j.archoralbio.2024.106136
10. Santos JL, Saus E, Smalley SV, Cataldo LR, Alberti G, Parada J, et al. Copy Number Polymorphism of the Salivary Amylase Gene: Implications in Human Nutrition Research. J Nutrigenet Nutrigenomics. 2012;5(3):117-131. doi:10.1159/000339951
11. Hashim NT, Fathima S, Hisham NM, Shivappa P, Magaogao MV, Islam MS, et al. Exploring Salivary Alpha-Amylase as a Biomarker in Periodontitis: A Comparative Analysis of Disease Stages and Clinical Correlations. Curr Issues Mol Biol. 2024 Nov;46(11):726. doi:10.3390/cimb46110726
12. Surdu A, Foia LG, Luchian I, Trifan D, Tatarciuc MS, Scutariu MM, et al. Saliva as a Diagnostic Tool for Systemic Diseases—A Narrative Review. Medicina. 2025 Feb;61(2):243. doi:10.3390/medicina61020243
13. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021 Mar 29;372:n71. doi:10.1136/bmj.n71
14. Falchi M, El-Sayed Moustafa JS, Takousis P, Pesce F, Bonnefond A, Andersson-Assarsson JC, et al. Low copy number of the salivary amylase gene predisposes to obesity. Nat Genet. 2014 May;46(5):492-497. doi:10.1038/ng.2939
15. Zhang X, Moran C, Wang R, Zhou Y. Effect of Aerobic Exercise in Chinese Adult Individuals at Risk for Type 2 Diabetes Mellitus (T2DM) with Low Salivary Amylase Gene (AMY1) Copy Number Variation. Diabetes Metab Syndr Obes. 2023 Jan;16:2875-2883. doi:10.2147/DMSO.S409007
16. Stangvaltaite-Mouhat L, Pūrienė A, Aleksejūnienė J, Stankeviciene I, Tommeras B, Al-Haroni M. Amylase Alpha 1 Gene (AMY1) Copy Number Variation and Dental Caries Experience: A Pilot Study among Adults in Lithuania. Caries Res. 2021 Mar;55(3):174-182. doi:10.1159/000514667
17. Hasegawa T, Kakuta M, Yamaguchi R, Sato N, Mikami T, Murashita K, et al. Impact of salivary and pancreatic amylase gene copy numbers on diabetes, obesity, and functional profiles of microbiome in Northern Japanese population. Sci Rep. 2022 May;12(1):7628. doi:10.1038/s41598-022-11730-7
18. Choi YJ, Nam YS, Yun JM, Park JH, Cho BL, Son HY, et al. Association between salivary amylase (AMY1) gene copy numbers and insulin resistance in asymptomatic Korean men. Diabet Med. 2015 Dec;32(12):1588-1595. doi:10.1111/dme.12808
19. Shin D, Lee KW. Dietary carbohydrates interact with AMY1 polymorphisms to influence the incidence of type 2 diabetes in Korean adults. Sci Rep. 2021 Aug;11(1):16788. doi:10.1038/s41598-021-96257-z
20. Kor M, Pouramir M, Khafri S, Ebadollahi S, Gharekhani S. Association between Dental Caries, Obesity and Salivary Alpha Amylase in Adolescent Girls of Babol City, Iran-2017. J Dent (Shiraz). 2021 Mar;22(1):27-32. doi:10.30476/DENTJODS.2020.84190.1070
21. Parsaie Z, Rezaie P, Azimi N, Mohammadi N. Relationship between Salivary Alpha-Amylase Enzyme Activity, Anthropometric Indices, Dietary Habits, and Early Childhood Dental Caries. Int J Dent. 2022;2022:2617197. doi:10.1155/2022/2617197
22. Padmanabhan V, Islam MS, Rahman MM, Goud MBK, Alshehhi LMSA, Hamed HMA, et al. Salivary alpha-amylase activity and its association with early childhood caries and rampant caries experience: a cross-sectional study. Front Med. 2024;11:1480139. doi:10.3389/fmed.2024.1480139
23. Perry GH, Dominy NJ, Claw KG, Lee AS, Fiegler H, Redon R, et al. Diet and the evolution of human amylase gene copy number variation. Nat Genet. 2007 Oct;39(10):1256-1260. doi:10.1038/ng2123
24. Hatipoğlu Ö, Saydam F. The role of AMY1 gene copy number variation in dental caries susceptibility: Insights from a Turkish population. BMC Oral Health. 2025;25:722. doi:10.1186/s12903-025-06074-3
25. Venkatapoorna CMK, Ayine P, Parra EP, Koenigs T, Phillips M, Babu JR, et al. Association of Salivary Amylase (AMY1) Gene Copy Number with Obesity in Alabama Elementary School Children. Nutrients. 2019 Jun;11(6):1379. doi:10.3390/nu11061379
26. Selvaraju V, Venkatapoorna CMK, Babu JR, Geetha T. Salivary Amylase Gene Copy Number Is Associated with the Obesity and Inflammatory Markers in Children. Diabetes Metab Syndr Obes. 2020 May;13:1695-1701. doi:10.2147/DMSO.S251359
27. Devarakonda SLS, Ren J, Poole AC. The association between salivary amylase gene copy number and enzyme activity with type 2 diabetes status. medRxiv. 2025 Mar 31;2025.03.31.25324922. doi:10.1101/2025.03.31.25324922
28. Khalifa O, Al-Akl NS, Arredouani A. Differential expression of cardiometabolic and inflammation markers and signaling pathways between overweight/obese Qatari adults with high and low plasma salivary α-amylase activity. Front Endocrinol. 2024;15:1421358. doi:10.3389/fendo.2024.1421358
29. Spatafora G, Li Y, He X, Cowan A, Tanner ACR. The Evolving Microbiome of Dental Caries. Microorganisms. 2024 Jan;12(1):121. doi:10.3390/microorganisms12010121
30. Farrell M, Ramne S, Gouinguenet P, Brunkwall L, Ericson U, Raben A, et al. Effect of AMY1 copy number variation and various doses of starch intake on glucose homeostasis: Data from a cross-sectional observational study and a crossover meal study. Genes Nutr. 2021 Nov;16(1):21. doi:10.1186/s12263-021-00701-8
31. Rukh G, Ericson U, Andersson-Assarsson J, Orho-Melander M, Sonestedt E. Dietary starch intake modifies the relation between copy number variation in the salivary amylase gene and BMI. Am J Clin Nutr. 2017 Jul;106(1):256-262. doi:10.3945/ajcn.116.149831
32. Zhan F, Chen J, Yan H, Wang S, Zhao M, Zhang S, et al. Association of Serum Amylase Activity and the Copy Number Variation of AMY1/2A/2B with Metabolic Syndrome in Chinese Adults. Diabetes Metab Syndr Obes. 2021 Dec;14:4705-4714. doi:10.2147/DMSO.S339604
33. Al-Akl NS, Thompson RI, Arredouani A. Reduced odds of diabetes associated with high plasma salivary α-amylase activity in Qatari women: A cross-sectional study. Sci Rep. 2021 Jun;11(1):11495. doi:10.1038/s41598-021-90977-y
34. Tayhan F, Helvacı G, Yabancı Ayhan N. Obesity Parameters in Women Is Associated With AMY1 Gene Copy Number, Nesfatin-1 Level, and Dietary Intake: A Case-Control Study. Mol Nutr Food Res. 2024;68(4):e70049. doi:10.1002/mnfr.70049
35. Rossi N, Aliyev E, Visconti A, Akil ASA, Syed N, Aamer W, et al. Ethnic-specific association of amylase gene copy number with adiposity traits in a large Middle Eastern biobank. NPJ Genom Med. 2021 Feb;6(1):1-9. doi:10.1038/s41525-021-00170-3
36. Yang ZM, Chen LH, Zhang M, Lin J, Zhang J, Chen WW, et al. Age Differences of Salivary Alpha-Amylase Levels of Basal and Acute Responses to Citric Acid Stimulation Between Chinese Children and Adults. Front Physiol. 2015 Oct;6:340. doi:10.3389/fphys.2015.00340
37. Mauricio-Castillo R, Valdevit A, Gonzalez-Davalos L, Dominguez-Perez RA, Garcia-Solis P, Vazquez-Martinez O, et al. Dental caries prevalence and severity positively associate with AMY1 gene copy number. Clin Oral Investig. 2023 Dec;28(1):25. doi:10.1007/s00784-023-05435-y
38. Carpenter D, Mitchell LM, Armour JAL. Copy number variation of human AMY1 is a minor contributor to variation in salivary amylase expression and activity. Hum Genomics. 2017 Feb;11(1):2. doi:10.1186/s40246-017-0097-3
39. Stankeviciene I, Puriene A, Brukiene V, Mieliauskaite D, Bække S, Tommeras B, et al. AMY1 gene copy number associated with xerostomia and Sjögren’s syndrome: A cross-sectional study. BMC Oral Health. 2025 Feb;25(1):239. doi:10.1186/s12903-025-05595-1
40. Poole AC, Goodrich JK, Youngblut ND, Luque GG, Ruaud A, Sutter JL, et al. Human Salivary Amylase Gene Copy Number Impacts Oral and Gut Microbiomes. Cell Host Microbe. 2019 Apr;25(4):553-564. doi:10.1016/j.chom.2019.03.001
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