Posted on 04/04/2014 at 01:02:04 PM by Student BloggerBy Colby Vorland
A new paper published this week in Nature Genetics adds to a complex and exciting scientific story about the gene(s) AMY1, which codes for salivary (alpha-)amylase, the first step in starch digestion in the mouth. The number of copies of AMY1 has been shown previously to correlate with how long populations have been exposed to dietary starch, suggesting an interesting example of selective pressure by the diet in a relatively short time frame (Perry et al., 2007). It would make sense that more AMY1 would therefore help to breakdown starch faster and increase blood glucose more than having fewer copies, to provide more energy to cultures surrounded by starch.
Alas, if only science were that easy. Mandel and Breslin published data in 2012 that showed just the opposite - more AMY1 and salivary amylase results in lower glucose concentrations after ingesting a starch solution compared to the low group. The greatest difference between the groups was about 40 mg/dL - a clinically relevant result. Even more interestingly, insulin overall was not different between the fewer and higher AMY1 groups. The authors hypothesize that insulin response in the first 15 minutes after a meal (cephalic phase) may increase more in the more AMY1 group and improve glucose control, yet not affect long-term insulin response, but this needs to be rigorously tested in future research. It is also interesting that the same lab found that salivary amylase amount and activity seems to influence textural perception of starch (viscosity), although AMY1 was not directly related (Mandel et al., 2010). Viscosity impacts food preference, adding another plot twist in this story that has yet to be fully told.
But back to the new entry in this page-turner. This time, Falchi and colleagues (2014) showed that AMY1 is related to obesity. In a Swedish population, they found that AMY1 copy number was associated with BMI and fat mass. In a meta-analysis of UK and French cohorts, reduced AMY1 copies were associated with increased BMI and obesity, and in a group of participants of Singaporean Chinese background, lower AMY1 was also associated with elevated obesity. Similarly in a separate French study, AMY1 copy number was associated with serum (total) amylase level and inversely to BMI, and AMY1 and AMY2 number correlated with salivary and pancreatic amylase level, which were inversely associated with BMI. In summary: fewer AMY1 copies, increased obesity risk.
AMY1 copy number had a stronger association with BMI than polymorphisms in FTO, which is the most replicated “obesity gene” to date. The authors estimated that AMY1 number explains between 1.73 and 7.94% of obesity, and 0.66 to 4.40% of BMI. Further, they estimated that this is 2.47 to 19.86% of obesity's estimated heritability of 40 to 70%. This is quite impressive for one gene. Interestingly, AMY1 is highly expressed in the adipose tissue, so future research will need to explore its role there.
The majority of the chapters of the AMY1 book remain to be written, but it seems to be one of the more interesting genetic interactions with diet. Though we can only speculate at this point, it is possible that starch recommendations could be personalized by copy number of AMY1 in the future, given that a low count seems to result in worsened glucose control and increased obesity risk should starch be mediating the latter. And of course, it gives us a little more insight into our considerable capacity for long-term adaptation to changing food environments.
Falchi, M, Moustafa, J, Takousis, P, Pesce, F, Bonnefond, A, Andersson-assarsson, J. C.Hammond, C. J. (2014). Low copy number of the salivary amylase gene predisposes to obesity. Nature Genetics. doi:10.1038/ng.2939
Mandel, A. L., des Gachons, C. P., Plank, K. L., Alarcon, S., & Breslin, P. A. (2010). Individual differences in AMY1 gene copy number, salivary α-amylase levels, and the perception of oral starch. PLoS ONE. 5(10), e13352.
Mandel, A. L., & Breslin, P. A. (2012). High endogenous salivary amylase activity is associated with improved glycemic homeostasis following starch ingestion in adults. The Journal of Nutrition. 142(5), 853-858.
Perry, G. H., Dominy, N. J., Claw, K. G., et al (2007). Diet and the evolution of human amylase gene copy number variation. Nature Genetics, 39(10), 1256-1260.