Gene Variation Drives Up Salivary Enzymes in Diabetics
New research indicates a common genetic variation can significantly increase salivary enzyme production, particularly in individuals with diabetes, suggesting a potential biological connection between starch digestion and blood sugar control.
The Role of AMY1 Gene Copy Number
Variations in copy number (CN) signify differences in the number of copies of a specific DNA sequence among individuals. Affecting approximately 10% of the human genome, these variants influence gene expression, thus contributing to varying physical traits and disease susceptibility.
One prevalent CNV involves the AMY1 gene, responsible for encoding salivary amylase, an enzyme that initiates starch breakdown in the oral cavity. In humans, the diploid AMY1 CN spans from 2 to 20, potentially impacting an individual’s metabolic profile.
Study Design and Participant Demographics
The research featured two groups: healthy adults participating in a starch study and individuals aged 45 and older with self-reported prediabetes or type 2 diabetes from a T2D microbiome study. Participants were recruited from the Ithaca, USA area.
Saliva samples from 196 participants were analyzed to ascertain AMY1 CN, while samples from a subset of 94 participants were used to measure SAA. Genomic DNA was extracted from saliva to measure AMY1 CN using qPCR and ddPCR techniques.
Key Findings: AMY1 CN and SAA
The median AMY1 CN, as determined by qPCR, was 7.5 (ranging from 2 to 19 copies) and by ddPCR, it was 7.0 (ranging from 2 to 20 copies). A linear mixed model revealed that SAA levels increased as the day progressed, which aligns with previous findings indicating a surge in SAA from morning to midday.
Interestingly, the study found that AMY1 CN could independently account for 18% of the variance in SAA. Researchers suggest that other biological or unexamined factors may contribute to the variance in SAA.
Association with Type 2 Diabetes
A noteworthy association emerged between AMY1 CN and T2D/prediabetes status. For each additional copy of AMY1, SAA increased by nearly 14% in the control group and 43% in the T2D/prediabetes group.
According to the CDC, in 2019, 37.3 million US adults had diabetes; 28.3 million were diagnosed, and 9.0 million were undiagnosed (CDC 2020).
Implications and Future Research
The researchers propose that higher SAA levels might either alleviate or exacerbate glucose dysregulation in individuals with T2D, but emphasize the necessity for longitudinal studies to establish the directionality of this relationship.
Furthermore, the study underscores the importance of consistent saliva collection timing for accurate SAA interpretation as a biomarker, given its natural daily fluctuations.
Conclusions and Considerations
While both qPCR and ddPCR methods proved effective in measuring AMY1 CN, caution is advised when drawing causal inferences due to the study’s cross-sectional design and limited number of participants with T2D/prediabetes.
Ultimately, further investigation is warranted to fully elucidate the role of SAA in glucose homeostasis and its potential health applications. Future studies should prioritize the timing of saliva collection, dietary context, and other relevant factors in establishing SAA as a reliable health biomarker.
