Background: Metabolic syndrome (MetS), a cluster of metabolic and cardiovascular risk factors is influenced by environmental, lifestyle, and genetic factors. We explored whether coffee consumption and the rs301 variant of the lipoprotein lipase (LPL) gene are related to MetS. Methods: We conducted multiple logistic regression analyses using data gathered from 9523 subjects in Taiwan Biobank (TWB). Results: Our findings indicated that individuals who consumed coffee had a reduced odds ratio (OR) for MetS (0.750 (95% confidence interval [CI] 0.653–0.861) compared to non-coffee drinkers. Additionally, the risk of MetS was lower for individuals with the 'TC' and 'CC' genotypes of rs301 compared to those with the 'TT' genotype. Specifically, the OR for MetS was 0.827 (95% CI 0.721–0.949) for the 'TC' genotype and 0.848 (95% CI 0.610–1.177) for the 'CC' genotype. We observed an interaction between coffee consumption and the rs301 variant, with a p-value for the interaction of 0.0437. Compared to the reference group ('no coffee drinking/TT'), the ORs for MetS were 0.836 (95% CI 0.706–0.992) for 'coffee drinking/TT', 0.557 (95% CI 0.438–0.707) for 'coffee drinking/TC', and 0.544 (95% CI 0.319–0.927) for 'coffee drinking/CC'. Notably, MetS was not observed in non-coffee drinkers regardless of their rs301 genotype. Conclusion: Our findings suggest that rs301 genotypes may protect against MetS in Taiwanese adults who consume coffee compared to non-coffee drinkers.
Keywords: Metabolic syndrome; Polymorphism; Coffee
Metabolic syndrome is a severe condition characterized by the presence of at least 3 of the following components: central adiposity, elevated fasting glucose, blood pressure, triglycerides (TGs), and low plasma levels of high-density lipoprotein (HDL) cholesterol [[
Notably, the prevalence of this multifactorial disorder is increasing worldwide. Genetics, lifestyle, and environmental factors are essential to understanding the interactions between the various components associated with MetS [[
Metabolic risk components are widely recognized as being inherited and several genetic variants have already been investigated for MetS. One gene that has been implicated in metabolic syndrome is the LPL gene, which encodes for lipoprotein lipase, an enzyme involved in the metabolism of lipids. A specific variant of this gene, rs301 has been associated with metabolic syndrome and its components in diverse populations [[
It has been suggested that individual genetic profiles might influence how the body metabolizes coffee [[
In the current study, we analyzed TWB data for 9523 subjects assessed at recruitment centers across Taiwan between 2008 and 2016. Before the assessment, participants had provided written informed consent. Following the completion of the questionnaires, they were examined physically and blood samples were collected for DNA analysis. Of the overall subjects enrolled in the current study, we excluded 1662 subjects with missing data (i.e., those with incomplete questionnaires and missing genotype data). The final analysis involved 7861 eligible subjects. None of these subjects had a cancer diagnosis in the past. We obtained approval for this study from the institutional review board of Cheng Ching Hospital (HP200012).
Subjects were identified as having metabolic syndrome if they displayed a minimum of 3 of the following characteristics: waist circumference of ≥ 90 cm (35 inches) for men or ≥ 80 cm (31 inches) for women, systolic blood pressure ≥ 130mmHg and diastolic blood pressure ≥ 85mmHg, or were actively on antihypertensive medication, fasting blood glucose ≥ 100 mg/dL, or were receiving treatment for diabetes, fasting triglyceride ≥ 150 mg/dL or were currently receiving treatment for hypertriglyceridemia, and HDL-C < 40 mg/dL for men or < 50 mg/dL for women. These criteria are based on the scientific statement on MS diagnosis issued by the American Heart Association and National Heart, Lung, and Blood Institute [[
Lifestyle data were gathered through questionnaires administered to each participant at the time of initial assessment at each center. These factors, which have also been explored previously for metabolic syndrome [[
Using search engines like Science Direct, PubMed, Snpedia, and Google Scholar, we chose variant rs301 of the LPL gene. Because of its association with metabolic syndrome and its components, it was deemed appropriate to include it in the study. Details on sample collection and genotyping are available on the TWB website [[
We employed SAS software (version 9.4, SAS Institute, Cary, NC, USA) and PLINK v1.90 for our data analyses. We stratified baseline variables based on coffee consumption and presented data as numbers and percentages. Categorical variables were compared using the Chi-square (χ2) test, and we determined genotypic associations using multiple logistic regression analysis.
The baseline characteristics of participants are presented in Table 1. Metabolic syndrome was identified in about 16.2% (n = 427) of those who drank coffee. Female coffee drinkers were more than male drinkers (55.14% vs. 44.86%). Of the overall samples, the OR for MetS in coffee drinkers compared with nondrinkers was 0.750 (95% CI 0.653–0.861) as shown in Table 2. Compared with 'TT' of rs301, the OR for MetS was 0.827 (95% CI 0.721–0.949) and 0.848 (95% CI 0.610–1.177) for 'TC and CC,' respectively. The corresponding ORs were 1.825 (95% CI 1.507–2.209), 3.123 (95% CI 2.582–3.778), and 4.464 (95% CI 3.603–5.529) for the 41 to 50, 51 to 60, and 61 to 70 compared to the 30 to 40 year age group. Overweight, obese, and smoking individuals had ORs of 3.943 (95% CI 3.323–4.678), 14.600 (95% CI 12.266–17.378), and 1.564 (95% CI 1.275–1.917), respectively. There was an interaction between coffee drinking and rs301 (p for interaction = 0.0437). After stratification (Tables 3 and 4), coffee drinkers carrying 'TT, TC, and CC' genotypes had ORs of 0.852 (95% CI 0.718–1.011), 0.599 (95% CI 0.463–0.774), and 0.477 (95% CI 0.229–0.992), respectively. With the no coffee drinking and 'TT' group used as the reference group, significant ORs were 0.836 (95% CI 0.706–0.992) for 'coffee drinking/TT,' 0.557 (95% CI 0.438–0.707) for coffee with 'TC,' and 0.544 (95% CI 0.319–0.927) for 'coffee drinking/CC,' respectively (Table 4). MetS was not observed among non-coffee drinkers, no matter the rs301 genotype.
Table 1 Baseline characteristics of the study subjects
No coffee consumption Coffee consumption p-value ( ( < 0.001 No 4165(79.70) 2208(83.80) Yes 1061(20.30) 427(16.20) 0.009 TT 3306(63.26) 1671(63.42) TC 1737(33.24) 836(31.73) CC 183(3.50) 128(4.86) < 0.001 Female 2619(50.11) 1453(55.14) Male 2607(49.89) 1182(44.86) < 0.001 30 to 40 1414(27.06) 785(29.79) 41 to 50 1430(27.36) 849(32.22) 51 to 60 1499(28.68) 669(25.39) 61 to 70 883(16.90) 332(12.60) 0.176 Normal 2554(48.87) 1255(47.63) Overweight 1577(30.18) 849(32.22) Obese 1095(20.95) 531(20.15) 0.001 Never 4064(77.77) 1946(73.85) Former 591(11.31) 340(12.90) Current 571(10.93) 349(13.24) 0.392 Never 4693(89.80) 2347(89.07) Former 155(2.97) 75(2.85) Current 378(7.23) 213(8.08) 0.002 No 3348(64.06) 1691(64.17) Aerobic 1687(32.28) 805(30.55) Non aerobic 191(3.65) 139(5.28) 0.072 No 3609(69.06) 1767(67.06) Yes 1617(30.94) 868(32.94) < 0.001 No 4692(89.78) 2426(92.07) Former 276(5.28) 82(3.11) Current 258(4.94) 127(4.82)
Data were presented as numbers and percentages. Abbreviation: MetS = Metabolic Syndrome, BMI = body mass index; TT, TC, and CC are the genotypes of the variant rs301
Table 2 The odds of metabolic syndrome among study subjects
OR 95% CI Yes 0.750 0.653–0.861 < 0.001 TC 0.827 0.721–0.949 0.007 CC 0.848 0.610–1.177 0.325 Male 0.855 0.737–0.992 0.039 41 to 50 1.825 1.507–2.209 < 0.001 51 to 60 3.123 2.582–3.778 < 0.001 61 to 70 4.464 3.603–5.529 < 0.001 Overweight 3.943 3.323–4.678 < 0.001 Obese 14.600 12.266–17.378 < 0.001 Former 0.931 0.758–1.143 0.494 Current 1.564 1.275–1.917 < 0.001 Former 1.420 1.025–1.964 0.034 Current 1.257 0.997–1.586 0.053 Aerobic 0.852 0.738–0.983 0.028 Non-Aerobic 0.787 0.564–1.099 0.159 Yes 1.176 1.024–1.350 0.022 Former 1.166 0.851–1.596 0.339 Current 0.974 0.722–1.315 0.866
Abbreviation: OR = odds ratio; ref = reference; BMI = body mass index; TT, TC, and CC are the genotypes of the variant rs301.
Table 3 Risk of metabolic syndrome among subjects based on stratification by genotypes of the rs301 variant
TT TC CC OR 95% CI p-value OR 95% CI p-value OR 95% CI p-value Yes 0.852 0.718–1.011 0.067 0.599 0.463–0.774 < 0.001 0.477 0.229–0.992 0.047 Male 0.941 0.782–1.132 0.517 0.738 0.564–0.965 0.027 0.447 0.187–1.069 0.070 41 to 50 1.814 1.431–2.299 < 0.001 2.051 1.441–2.920 < 0.001 0.661 0.240–1.821 0.423 51 to 60 3.133 2.471–3.972 < 0.001 3.507 2.477–4.966 < 0.001 1.731 0.701–4.277 0.234 61 to 70 4.650 3.558–6.077 < 0.001 4.711 3.186–6.967 < 0.001 2.551 0.887–7.332 0.082 Overweight 3.647 2.954–4.503 < 0.001 4.560 3.335–6.233 < 0.001 5.279 2.077–13.415 0.001 Obese 14.989 12.097–18.571 < 0.001 14.116 10.231–19.478 < 0.001 22.899 8.576–61.141 < 0.001 Former 0.766 0.591–0.992 0.043 1.325 0.925–1.898 0.125 1.192 0.334–4.261 0.787 Current 1.333 1.031–1.725 0.029 2.040 1.424–2.923 < 0.001 4.609 1.538–13.813 0.006 Former 1.962 1.319–2.919 0.001 0.906 0.482–1.696 0.757 0.137 0.020–0.937 0.043 Current 1.193 0.886–1.607 0.246 1.492 1.001–2.222 0.049 0.659 0.206–2.109 0.482 Aerobic 0.858 0.719–1.025 0.091 0.790 0.609–1.024 0.075 1.099 0.506–2.386 0.811 Non-Aerobic 0.777 0.511–1.181 0.237 0.761 0.419–1.383 0.370 0.582 0.103–3.281 0.540 Yes 1.192 1.004–1.415 0.045 1.087 0.846–1.395 0.514 1.571 0.716–3.448 0.260 Former 1.398 0.947–2.066 0.092 0.943 0.542–1.644 0.837 0.274 0.035–2.125 0.216 Current 1.042 0.716–1.516 0.830 0.972 0.572–1.652 0.917 0.280 0.041–1.896 0.192
Abbreviation: OR = odds ratio; ref = reference; BMI = body mass index; TT, TC, and CC are the genotypes of the variant rs301
Table 4 Risk of metabolic syndrome based on coffee consumption and genotypes of rs301
OR 95% CI p-value No coffee drinking/TC 0.903 0.768–1.063 0.222 No coffee drinking/CC 0.986 0.653–1.488 0.945 Coffee drinking/TT 0.836 0.706–0.991 0.039 Coffee drinking/TC 0.557 0.438–0.707 < 0.001 Coffee drinking/CC 0.544 0.319–0.927 0.025
Abbreviation: OR = odds ratio, ref = reference; TT, TC, and CC are the genotypes of the variant rs301 Adjusted for sex, age, BMI, smoking, alcohol consumption, exercise, midnight snacking, and vegetarian diet
In our comprehensive examination involving 7861 subjects from the TWB, we uncovered intriguing associations between coffee consumption, the rs301 polymorphism of the LPL gene, and MetS. Notably, our investigation delved into the interplay between genetic predisposition and lifestyle choices in the context of MetS risk. We identified a protective effect of coffee consumption against MetS, a finding reinforced by the significant odds ratios associated with 'TT, TC, and CC' genotypes of the rs301 polymorphism.
Results from an earlier cross-sectional study implied that consuming a moderate amount of coffee, ranging from 1 to 4 cups per day, could enhance metabolic health [[
Recent reports from the Jakarta Post and an earlier publication [[
Additionally, we identified positive associations between older age, overweight, obesity, and smoking with MetS. Obesity is a commonly observed component of MetS [[
Our study's findings have certain implications for both public health policies and individual lifestyle decisions, particularly within populations exhibiting a high prevalence of the rs301 variant. The study suggests that individuals who consume coffee have a lower odds ratio for MetS compared to non-coffee drinkers. This finding aligns with existing research indicating potential health benefits associated with moderate coffee consumption, such as improved metabolic health and reduced cardiovascular risk [[
While our study boasts a sizable sample size, the limitation includes a lack of detailed information on caffeine intake and coffee preparation methods. Further research, encompassing diverse populations and exploring the molecular mechanisms underlying these associations, is warranted to validate and expand upon our findings.
In summary, the study suggests that the rs301 genotype may confer protection against MetS, particularly in the context of coffee consumption, and more so in older adults. These findings have the potential to inform personalized health strategies and contribute to the development of targeted interventions for metabolic health within specific populations.
The authors would like to thank Cheng Ching Hospital and the Ministry of Science and Technology for providing research grants.
Pao-Chun Hsieh, Oswald Ndi Nfor, Chih-Hsuan Hsiao, Chuan-Chao Lin, and Yung-Po Liaw conceived and designed the study. Chih-Hsuan Hsiao, Oswald Ndi Nfor, Chuan-Chao Lin, and Yung-Po Liaw analyzed and interpreted data. Pao-Chun Hsieh and Oswald Ndi Nfor drafted the manuscript text. All authors reviewed and approved the manuscript.
This project was funded by Cheng Ching General Hospital, Chung Kang Branch (CH10900246A) and in part by the Ministry of Science and Technology, Taiwan (MOST 108-2621-M-040-001). The funder was not involved in study design, data analysis, interpretation, or drafting of the manuscript.
The data that support the findings of this study are available from Taiwan Biobank but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of Taiwan Biobank.
Ethical approval for this work was granted by the Institutional Review Board of Cheng Ching Hospital (HP200012). Participants in the Taiwan Biobank gave written informed consent during recruitment.
Not applicable.
The authors declare no competing interests.
• MetS
- metabolic syndrome
• LPL
- lipoprotein lipase
• TWB
- Taiwan Biobank
• OR
- odds ratio
• CI
- confidence interval
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By Pao-Chun Hsieh; Oswald Ndi Nfor; Chuan-Chao Lin; Chih-Hsuan Hsiao and Yung-Po Liaw
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