J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Original Article

Volume 12, Number 3, March 2020, pages 184-189

Copy Number Variation of the Salivary Amylase Gene and Glucose Metabolism in Healthy Young Japanese Women

Figure 1. Levels of blood glucose after starch loading. Data are expressed as the mean ± SD. *P < 0.05, t-test, high vs. low AMY1 CNV. High AMY1 CNV: 8 - 14; low AMY1 CNV: 4 - 7. SD: standard deviation; CNV: copy number variation; AMY1: salivary amylase gene.

Figure 2. Changes of blood glucose from baseline after starch loading. Data are expressed as the mean ± SD. High AMY1 CNV: 8 - 14; low AMY1 CNV: 4 - 7. SD: standard deviation; CNV: copy number variation; AMY1: salivary amylase gene.

**Table 1.** Characteristics of the Study Participants
Characteristics	Means ± SD or median (IQ)
Divided by the protein concentration in each saliva sample. SD: standard deviation; BMI: body mass index; HDL-C: high-density lipoprotein cholesterol; HbA1c: glycated hemoglobin; AMY1*: salivary amylase gene; CNV: copy number variation; IQ: interquartile range; TG: triglycerides; FPG: fasting plasma glucose.
Age (years)	23.0 ± 4.2
BMI, kg/m² (range)	20.1 ± 1.6 (17.5 - 24.3)
TG, mg/dL (IQ)	52 (38 - 68)
HDL-C, mg/dL	73 ± 15.7
HbA1c, % (range)	5.25 ± 0.19 (4.9-5.6%)
mmol/mol (range)	33 (30 - 37)
Total ketone bodies, µmol/L (IQ)	39.5 (29 - 66)
3-Hydroxybutyric acid, µmol/L (IQ)	24 (15.5 - 42)
Acetoacetic acid, µmol/L (IQ)	17 (11.5 - 24)
Respiratory quotient	0.77 ± 0.05
Energy consumption, kcal	1737 ± 350
Carbohydrate energy, % in total energy	52.8 ± 5.2
Alcohol consumption, kcal (IQ)	14 (0.0 - 29.0)
AMY1 CNV (range)	8.3 ± 2.3 (4 - 14)
Salivary amylase, (U/L) IQ*	100 (62 - 148)
Total serum amylase (U/L)	91 ± 27.9
Serum salivary amylase(U/L)	61.3 ± 25.5
Serum pancreatic amylase (U/L)	29.9 ± 10.4
Percentage of serum salivary amylase (range)	66.0 ± 10.8 (40 - 86)

Table 1. Characteristics of the Study Participants

Characteristics

Means ± SD or median (IQ)

*Divided by the protein concentration in each saliva sample. SD: standard deviation; BMI: body mass index; HDL-C: high-density lipoprotein cholesterol; HbA1c: glycated hemoglobin; AMY1: salivary amylase gene; CNV: copy number variation; IQ: interquartile range; TG: triglycerides; FPG: fasting plasma glucose.

Age (years)

23.0 ± 4.2

BMI, kg/m² (range)

20.1 ± 1.6 (17.5 - 24.3)

TG, mg/dL (IQ)

52 (38 - 68)

HDL-C, mg/dL

73 ± 15.7

HbA1c, % (range)

5.25 ± 0.19 (4.9-5.6%)

mmol/mol (range)

33 (30 - 37)

Total ketone bodies, µmol/L (IQ)

39.5 (29 - 66)

3-Hydroxybutyric acid, µmol/L (IQ)

24 (15.5 - 42)

Acetoacetic acid, µmol/L (IQ)

17 (11.5 - 24)

Respiratory quotient

0.77 ± 0.05

Energy consumption, kcal

1737 ± 350

Carbohydrate energy, % in total energy

52.8 ± 5.2

Alcohol consumption, kcal (IQ)

14 (0.0 - 29.0)

AMY1 CNV (range)

8.3 ± 2.3 (4 - 14)

Salivary amylase, (U/L) IQ*

100 (62 - 148)

Total serum amylase (U/L)

91 ± 27.9

Serum salivary amylase(U/L)

61.3 ± 25.5

Serum pancreatic amylase (U/L)

29.9 ± 10.4

Percentage of serum salivary amylase (range)

66.0 ± 10.8 (40 - 86)

**Table 2.** Correlation Coefficients Between the Study Parameters
	AMY1 CNV	Salivary amylase	Serum amylase	RQ
P < 0.05; P < 0.01; *P < 0.001. AMY1*: salivary amylase gene; CNV: copy number variation; RQ: respiratory quotient; BMI: body mass index; HDL-C: high-density lipoprotein cholesterol; HbA1c: glycated hemoglobin.
BMI	-0.02	0.02	-0.29*	-0.22	-0.18	0.01	0.09
HbA1c	-0.36**	-0.13	-0.17	-0.30*	0.14	-0.37**	-0.12
Triglyceride	-0.15	0.23	-0.04	-0.05	-0.01	-0.04	0.10
HDL-C	-0.14	-0.17	-0.16	-0.20	0.06	-0.17	0.02
Uric acid	0.29*	0.09	-0.09	-0.06	-0.07	0.05	-0.15
Total ketone bodies	0.14	-0.04	-0.14	-0.10	-0.15	0.1	-0.44***
Acetoacetic acid	0.11	-0.01	-0.16	-0.13	-0.12	0.06	-0.36**
3-Hydroxybutyric acid	0.17	-0.06	-0.09	-0.05	-0.15	0.14	-0.45***
AMY1 CNV	-	-	-	-	-	-	-
Salivary amylase	0.39**	-	-	-	-	-	-
Serum amylase
Total	0.29*	0.34**	-	-	-	-	-
Salivary	0.36**	0.36**	0.91***	-	-	-	-
Pancreatic	-0.08	0.13	0.40**	0.04	-	-	-
% Salivary	0.37**	0.24	0.36**	0.68***	-0.64***	-	-
RQ	-0.06	-0.02	0.21	0.12	0.29*	-0.13	-
Blood glucose time course
Baseline	-0.14	-0.12	-0.11	-0.18	0.15	-0.22	0.08
10 min	-0.05	0.08	-0.03	0.02	-0.25	0.13	0.15
30 min	0.05	0.11	0.17	0.26*	-0.18	0.38**	0.11
45 min	-0.02	-0.06	0.04	0.14	-0.22	0.27*	-0.07
60 min	-0.14	0.04	-0.20	-0.10	-0.22	0.16	-0.18
120 min	-0.07	-0.02	-0.08	-0.07	0.003	-0.04	-0.09

Table 2. Correlation Coefficients Between the Study Parameters

AMY1 CNV

Salivary amylase

Serum amylase

Total

Salivary

Pancreatic

% Salivary

*P < 0.05; **P < 0.01; ***P < 0.001. AMY1: salivary amylase gene; CNV: copy number variation; RQ: respiratory quotient; BMI: body mass index; HDL-C: high-density lipoprotein cholesterol; HbA1c: glycated hemoglobin.

BMI

-0.02

0.02

-0.29*

-0.22

-0.18

0.01

0.09

HbA1c

-0.36**

-0.13

-0.17

-0.30*

0.14

-0.37**

-0.12

Triglyceride

-0.15

0.23

-0.04

-0.05

-0.01

-0.04

0.10

HDL-C

-0.14

-0.17

-0.16

-0.20

0.06

-0.17

0.02

Uric acid

0.29*

0.09

-0.09

-0.06

-0.07

0.05

-0.15

Total ketone bodies

0.14

-0.04

-0.14

-0.10

-0.15

0.1

-0.44***

Acetoacetic acid

0.11

-0.01

-0.16

-0.13

-0.12

0.06

-0.36**

3-Hydroxybutyric acid

0.17

-0.06

-0.09

-0.05

-0.15

0.14

-0.45***

AMY1 CNV

Salivary amylase

0.39**

Serum amylase

Total

0.29*

0.34**

Salivary

0.36**

0.91***

Pancreatic

-0.08

0.13

0.40**

0.04

% Salivary

0.37**

0.24

0.36**

0.68***

-0.64***

-0.06

-0.02

0.21

0.12

0.29*

-0.13

Blood glucose time course

Baseline

-0.14

-0.12

-0.11

-0.18

0.15

-0.22

0.08

10 min

-0.05

0.08

-0.03

0.02

-0.25

0.13

0.15

30 min

0.05

0.11

0.17

0.26*

-0.18

0.38**

0.11

45 min

-0.02

-0.06

0.04

0.14

-0.22

0.27*

-0.07

60 min

-0.14

0.04

-0.20

-0.10

-0.22

0.16

-0.18

120 min

-0.07

-0.02

-0.08

-0.07

0.003

-0.04

-0.09

**Table 3.** Odds Ratios of Low *AMY1* CNV for High HbA1c
	High AMY1 CNV (8 - 14) (N = 40)	Low AMY1 CNV (4 - 7) (N = 20)
High HbA1c ≥ 5.4% (34 mmol/mol), n (%)	10 (25)	11 (55)
Model 1: unadjusted. Model 2: adjusted for age and BMI. Model 3: model 2 plus adjustments for energy consumption (kcal) and serum total amylase. Model 4: model 2 plus adjustments for energy consumption (kcal) and salivary amylase for its concentration. AMY1: salivary amylase gene; CNV: copy number variation; CI: confidence interval; HbA1c: glycated hemoglobin; BMI: body mass index.
Model 1	1 (reference)	3.67 (1.18 - 11.4)	0.02
Model 2	1 (reference)	4.32 (1.36 - 31.8)	0.02
Model 3	1 (reference)	6.31 (1.34 - 29.8)	0.02
Model 4	1 (reference)	8.31 (1.81 - 36.6)	0.006

Table 3. Odds Ratios of Low AMY1 CNV for High HbA1c

High AMY1 CNV (8 - 14) (N = 40)

Low AMY1 CNV (4 - 7) (N = 20)

High HbA1c ≥ 5.4% (34 mmol/mol), n (%)

10 (25)

11 (55)

Odds ratios (95% CI)

P values

Model 1: unadjusted. Model 2: adjusted for age and BMI. Model 3: model 2 plus adjustments for energy consumption (kcal) and serum total amylase. Model 4: model 2 plus adjustments for energy consumption (kcal) and salivary amylase for its concentration. AMY1: salivary amylase gene; CNV: copy number variation; CI: confidence interval; HbA1c: glycated hemoglobin; BMI: body mass index.

Model 1

1 (reference)

3.67 (1.18 - 11.4)

0.02

Model 2

1 (reference)

4.32 (1.36 - 31.8)

0.02

Model 3

1 (reference)

6.31 (1.34 - 29.8)

0.02

Model 4

1 (reference)

8.31 (1.81 - 36.6)

0.006