Interaction of energy and sulfur microbial diet and smoking status with polygenic variants associated with lipoprotein metabolism
IntroductionHypo-high-density lipoprotein cholesterolemia (hypo-HDL-C) contributes to the development of cardiovascular diseases. The hypothesis that the polygenic variants associated with hypo-HDL-C interact with lifestyle factors was examined in 58,701 middle-aged Korean adults who participated in...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-10-01
|
| Series: | Frontiers in Nutrition |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnut.2023.1244185/full |
| _version_ | 1797666500544299008 |
|---|---|
| author | Haeng Jeon Hur Hye Jeong Yang Min Jung Kim Kyunhee Lee Kyunhee Lee Dai Ja Jang Myung-Sunny Kim Myung-Sunny Kim Sunmin Park Sunmin Park |
| author_facet | Haeng Jeon Hur Hye Jeong Yang Min Jung Kim Kyunhee Lee Kyunhee Lee Dai Ja Jang Myung-Sunny Kim Myung-Sunny Kim Sunmin Park Sunmin Park |
| author_sort | Haeng Jeon Hur |
| collection | DOAJ |
| description | IntroductionHypo-high-density lipoprotein cholesterolemia (hypo-HDL-C) contributes to the development of cardiovascular diseases. The hypothesis that the polygenic variants associated with hypo-HDL-C interact with lifestyle factors was examined in 58,701 middle-aged Korean adults who participated in the Korean Genome and Epidemiology Study (KoGES).MethodsParticipants were categorized into the Low-HDL (case; n = 16,980) and Normal-HDL (n = 41,721) groups. The participants in the Low-HDL group were selected using the guideline-based cutoffs for hypo-HDL-C (<40 mg/dL for men and < 50 mg/dL for women) and included those taking medication for dyslipidemia. The genes associated with hypo-HDL-C were determined through a genome-wide association study (GWAS) in a city hospital-based cohort, and the results were validated in the Ansan/Anung study. The genetic variants for the single nucleotide polymorphism (SNP)-SNP interaction were selected using a generalized multifactor dimensionality reduction analysis, and the polygenic risk score (PRS) generated was evaluated for interaction with lifestyle parameters.ResultsThe participants with hypo-HDL-C showed a 1.45 and 1.36-fold higher association with myocardial infarction and stroke, respectively. The High-PRS with four SNPs, namely ZPR1_rs3741297, CETP_rs708272, BUD13_rs180327, and ALDH1A2_rs588136, and that with the 11q23.3 haplotype were positively associated with hypo-HDL-C by about 3 times, which was a 2.4-fold higher association than the PRS of 24 SNP with p < 5×10−8. The risk alleles of CETP_rs708272 and ALDH1A2_rs588136 were linked to increased expression in the heart and decreased in the brain, respectively. The selected SNPs were linked to the reverse cholesterol transport pathway, triglyceride-rich lipoprotein particle remodeling pathway, cholesterol storage, and macrophage-derived foam cell differentiation regulation. The PRS of the 4-SNP model interacted with energy intake and smoking status, while that of the haplotype interacted with a glycemic index of the diet, sulfur microbial diet, and smoking status.DiscussionAdults with a genetic risk for hypo-HDL-C need to modulate their diet and smoking status to reduce their risk. |
| first_indexed | 2024-03-11T19:59:18Z |
| format | Article |
| id | doaj.art-3a753ce923b747c0a1c000bb1aa7c282 |
| institution | Directory Open Access Journal |
| issn | 2296-861X |
| language | English |
| last_indexed | 2024-03-11T19:59:18Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Nutrition |
| spelling | doaj.art-3a753ce923b747c0a1c000bb1aa7c2822023-10-04T09:38:23ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2023-10-011010.3389/fnut.2023.12441851244185Interaction of energy and sulfur microbial diet and smoking status with polygenic variants associated with lipoprotein metabolismHaeng Jeon Hur0Hye Jeong Yang1Min Jung Kim2Kyunhee Lee3Kyunhee Lee4Dai Ja Jang5Myung-Sunny Kim6Myung-Sunny Kim7Sunmin Park8Sunmin Park9Food Functionality Research Division, Korea Food Research Institute, Wanju-gun, Jeollabuk-do, Republic of KoreaFood Functionality Research Division, Korea Food Research Institute, Wanju-gun, Jeollabuk-do, Republic of KoreaFood Functionality Research Division, Korea Food Research Institute, Wanju-gun, Jeollabuk-do, Republic of KoreaFood Functionality Research Division, Korea Food Research Institute, Wanju-gun, Jeollabuk-do, Republic of KoreaDepartment of Food Biotechnology, University of Science & Technology, Wanju-gun, Jeollabuk-do, Republic of KoreaFood Functionality Research Division, Korea Food Research Institute, Wanju-gun, Jeollabuk-do, Republic of KoreaFood Functionality Research Division, Korea Food Research Institute, Wanju-gun, Jeollabuk-do, Republic of KoreaDepartment of Food Biotechnology, University of Science & Technology, Wanju-gun, Jeollabuk-do, Republic of KoreaDepartment of Food and Nutrition, Obesity, Diabetes Research Center, Hoseo University, Asan-si, Republic of KoreaR&D, Yejunbio, Asan-si, Republic of KoreaIntroductionHypo-high-density lipoprotein cholesterolemia (hypo-HDL-C) contributes to the development of cardiovascular diseases. The hypothesis that the polygenic variants associated with hypo-HDL-C interact with lifestyle factors was examined in 58,701 middle-aged Korean adults who participated in the Korean Genome and Epidemiology Study (KoGES).MethodsParticipants were categorized into the Low-HDL (case; n = 16,980) and Normal-HDL (n = 41,721) groups. The participants in the Low-HDL group were selected using the guideline-based cutoffs for hypo-HDL-C (<40 mg/dL for men and < 50 mg/dL for women) and included those taking medication for dyslipidemia. The genes associated with hypo-HDL-C were determined through a genome-wide association study (GWAS) in a city hospital-based cohort, and the results were validated in the Ansan/Anung study. The genetic variants for the single nucleotide polymorphism (SNP)-SNP interaction were selected using a generalized multifactor dimensionality reduction analysis, and the polygenic risk score (PRS) generated was evaluated for interaction with lifestyle parameters.ResultsThe participants with hypo-HDL-C showed a 1.45 and 1.36-fold higher association with myocardial infarction and stroke, respectively. The High-PRS with four SNPs, namely ZPR1_rs3741297, CETP_rs708272, BUD13_rs180327, and ALDH1A2_rs588136, and that with the 11q23.3 haplotype were positively associated with hypo-HDL-C by about 3 times, which was a 2.4-fold higher association than the PRS of 24 SNP with p < 5×10−8. The risk alleles of CETP_rs708272 and ALDH1A2_rs588136 were linked to increased expression in the heart and decreased in the brain, respectively. The selected SNPs were linked to the reverse cholesterol transport pathway, triglyceride-rich lipoprotein particle remodeling pathway, cholesterol storage, and macrophage-derived foam cell differentiation regulation. The PRS of the 4-SNP model interacted with energy intake and smoking status, while that of the haplotype interacted with a glycemic index of the diet, sulfur microbial diet, and smoking status.DiscussionAdults with a genetic risk for hypo-HDL-C need to modulate their diet and smoking status to reduce their risk.https://www.frontiersin.org/articles/10.3389/fnut.2023.1244185/fullhypo-HDL-cholesterolemiacardiovascular diseasesenergy intakesulfur microbial diettriglyceridesreverse cholesterol transport |
| spellingShingle | Haeng Jeon Hur Hye Jeong Yang Min Jung Kim Kyunhee Lee Kyunhee Lee Dai Ja Jang Myung-Sunny Kim Myung-Sunny Kim Sunmin Park Sunmin Park Interaction of energy and sulfur microbial diet and smoking status with polygenic variants associated with lipoprotein metabolism Frontiers in Nutrition hypo-HDL-cholesterolemia cardiovascular diseases energy intake sulfur microbial diet triglycerides reverse cholesterol transport |
| title | Interaction of energy and sulfur microbial diet and smoking status with polygenic variants associated with lipoprotein metabolism |
| title_full | Interaction of energy and sulfur microbial diet and smoking status with polygenic variants associated with lipoprotein metabolism |
| title_fullStr | Interaction of energy and sulfur microbial diet and smoking status with polygenic variants associated with lipoprotein metabolism |
| title_full_unstemmed | Interaction of energy and sulfur microbial diet and smoking status with polygenic variants associated with lipoprotein metabolism |
| title_short | Interaction of energy and sulfur microbial diet and smoking status with polygenic variants associated with lipoprotein metabolism |
| title_sort | interaction of energy and sulfur microbial diet and smoking status with polygenic variants associated with lipoprotein metabolism |
| topic | hypo-HDL-cholesterolemia cardiovascular diseases energy intake sulfur microbial diet triglycerides reverse cholesterol transport |
| url | https://www.frontiersin.org/articles/10.3389/fnut.2023.1244185/full |
| work_keys_str_mv | AT haengjeonhur interactionofenergyandsulfurmicrobialdietandsmokingstatuswithpolygenicvariantsassociatedwithlipoproteinmetabolism AT hyejeongyang interactionofenergyandsulfurmicrobialdietandsmokingstatuswithpolygenicvariantsassociatedwithlipoproteinmetabolism AT minjungkim interactionofenergyandsulfurmicrobialdietandsmokingstatuswithpolygenicvariantsassociatedwithlipoproteinmetabolism AT kyunheelee interactionofenergyandsulfurmicrobialdietandsmokingstatuswithpolygenicvariantsassociatedwithlipoproteinmetabolism AT kyunheelee interactionofenergyandsulfurmicrobialdietandsmokingstatuswithpolygenicvariantsassociatedwithlipoproteinmetabolism AT daijajang interactionofenergyandsulfurmicrobialdietandsmokingstatuswithpolygenicvariantsassociatedwithlipoproteinmetabolism AT myungsunnykim interactionofenergyandsulfurmicrobialdietandsmokingstatuswithpolygenicvariantsassociatedwithlipoproteinmetabolism AT myungsunnykim interactionofenergyandsulfurmicrobialdietandsmokingstatuswithpolygenicvariantsassociatedwithlipoproteinmetabolism AT sunminpark interactionofenergyandsulfurmicrobialdietandsmokingstatuswithpolygenicvariantsassociatedwithlipoproteinmetabolism AT sunminpark interactionofenergyandsulfurmicrobialdietandsmokingstatuswithpolygenicvariantsassociatedwithlipoproteinmetabolism |