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Abstract
Objective
The mGluR1 (metabotropic glutamate receptor 1) gene, a G protein–coupled receptor, is known to mediate perceptions of umami tastes. Genetic variation in taste receptors may influence dietary intake, and in turn have an impact on nutritional status and risk of chronic disease. We investigated the association of mGluR1 rs2814863 polymorphism with lipid profiles and cardiovascular disease (CVD) risk, together with their modulation by macronutrient intake in Korean adults.
Methods
The subjects consisted of 8,380 Koreans aged 40-69 years participating in the Anseong and Ansan Cohort Study, which was a part of the Korean Genome Epidemiology Study (KoGES). Data was collected using self-administered questionnaires, anthropometric measurements, and blood chemical analysis.
Results
Carriers of C allele at mGluR1 rs2814863 was associated with decreased high density lipoprotein cholesterol (HDL-C) and increased triglyceride as compared to carriers of TT. Also, carriers of the C allele showed higher fat intake and lower carbohydrate intake than those with carriers of TT. After adjustment for multiple testing using false-discovery rate method, the significant difference of HDL-C, triglyceride, dietary fat, and carbohydrate across genotypes disappeared. Gene-diet interaction effects between rs2814863 and macronutrients intake were not significantly associated with HDL-C and triglyceride levels. However, carriers of C allele demonstrated significantly higher odds of CVD {odds ratio=1.13, 95% CI=1.02-1.25} compared with carriers of TT.
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Table 1.
General characteristics of study subjects
BMI; body mass index, MET; metabolic equivalent task, HDL-C; high density lipoprotein cholesterol, LDL-C; low density lipoprotein cholesterol, HbA1c; Hemoglobin A1c, HOMA-IR; homeostasis model assessment of insulin resistance, MAF; Minor allele frequency, HWE; Hardy-Weinberg equilibrium.
The data represent the means±SEM and p values obtained in the independent t-test or chi-square test for differences between male and female participants (*p<0.001, †p<0.0001).
Fasting glucose, Fasting insulin, HOMA-IR were measured in 3,891 male and 4,251 female participants.
If triglycerides were <400 mg/dL, LDL-C=[Total cholesterol−{HDL-C+(triglyceride/5)}], and LDL-C was measured in 3,823 male and 4,309 female participants.
Table 2.
Comparison of characteristics according to mGluR1 rs2814863 genotype
| TT (n=3,286) | TC+CC (n=5,094) | p value | |
|---|---|---|---|
| Sex (Male/Female) | 48.3/51.7 | 47.2/52.8 | 0.341 |
| Age (years) | 52.2±0.2 | 52.1±0.1 | 0.669 |
| Height (cm) | 160.2±0.2 | 160.0±0.1 | 0.724 |
| Weight (kg) | 63.2±0.2 | 63.2±0.1 | 0.637 |
| Waist circumstance (cm) | 82.5±0.2 | 82.6±0.1 | 0.419 |
| BMI (kg/m2)* | 24.4 (22.5-26.4) | 24.5 (22.6-26.6) | 0.470 |
| Blood pressure (mm Hg) | |||
| Systolic | 116.8±0.3 | 117.4±0.3 | 0.083 |
| Diastolic | 74.7±0.2 | 75.0±0.2 | 0.158 |
| Alcohol intake (g/d)* | 9.7 (2.9-28.1) | 10.0 (2.9-27.9) | 0.792 |
| Exercise (MET-h/d) | 3.7±0.1 | 3.6±0.1 | 0.482 |
| Current smokers (%) | 24.8 | 25.9 | 0.069 |
| High school education (%) | 43.9 | 45.3 | 0.120 |
| Total cholesterol (mg/dL)* | 196 (173-222) | 197 (173-222) | 0.967 |
| HDL-C (mg/dL)* | 48 (42-56) | 47 (41-56) | 0.023 |
| LDL-C (mg/dL) | 120.4±0.6 | 120.2±0.5 | 0.788 |
| Triglycerides (mg/dL)* | 123 (87-181) | 127 (88-185) | 0.030 |
| HbA1c (%)* | 5.6 (5.3-5.9) | 5.6 (5.4-5.9) | 0.310 |
| Fasting glucose (mg/dL)* | 88 (83-95) | 88 (82-95) | 0.317 |
| Fasting insulin (μIU/mL)* | 6.9 (5.2-9.6) | 7.0 (5.1-9.5) | 0.352 |
| HOMA-IR (arbitrary units)* | 1.5 (1.1-2.2) | 1.5 (1.1-2.2) | 0.270 |
| Dietary intake | |||
| Energy intake (kcal) | 1916.2±9.7 | 1902.4±7.9 | 0.305 |
| Protein (% of energy)* | 13.2 (11.8-14.7) | 13.3 (11.9-14.9) | 0.077 |
| Fat (% of energy) | 14.1±0.1 | 14.4±0.2 | 0.009 |
| Carbohydrate (% of energy) | 71.3±0.1 | 71.0±0.1 | 0.016 |
BMI; body mass index, MET; metabolic equivalent task, HDL-C; high density lipoprotein cholesterol, LDL-C; low density lipoprotein cholesterol, HbA1c; Hemoglobin A1c, HOMA-IR; homeostasis model assessment of insulin resistance The data represent the means±SEM and p values obtained in the generalized linear model (GLM), with adjustment for age and gender.
Fasting glucose, Fasting insulin, HOMA-IR were measured in 3,891 male and 4,251 female participants.
If triglycerides were <400 mg/dl, LDL-C=[Total cholesterol−{HDL-C+(triglyceride/5)}], and LDL-C was measured in 3,202 individuals with the AA genotype and 4,940 with the AG+GG genotype.
Table 3.
Interaction between mGluR1 rs2814863 genotype and dietary intake on lipid profiles
HDL-C; high density lipoprotein cholesterol, LDL-C; low density lipoprotein cholesterol
The participants were categorized by total energy intake and the percentage of energy they obtained from their median levels of protein, fat, and carbohydrate.
The data represent the median (interquartile range) and p values obtained in the generalized linear model (GLM), p interactions obtained in logistic regression model after adjustment for age and gender.
Table 4.
Association between mGluR1 rs2814863 genotype and cardiovascular disease
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