Pleiotropic association of LIPC variants with lipid and urinary 8-hydroxy deoxyguanosine levels in a Taiwanese population
Abstract Background Hepatic lipase (HL, encoded by LIPC) is a glycoprotein primarily synthesized and secreted by hepatocytes. Previous studies had demonstrated that HL is crucial for reverse cholesterol transport and affects the metabolism, composition, and level of several lipoproteins. In current...
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| Format: | Article |
| Language: | English |
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BMC
2019-05-01
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| Series: | Lipids in Health and Disease |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12944-019-1057-9 |
| _version_ | 1818478709428977664 |
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| author | Ming-Sheng Teng Semon Wu Lung-An Hsu I-Shiang Tzeng Hsin-Hua Chou Cheng-Wen Su Yu-Lin Ko |
| author_facet | Ming-Sheng Teng Semon Wu Lung-An Hsu I-Shiang Tzeng Hsin-Hua Chou Cheng-Wen Su Yu-Lin Ko |
| author_sort | Ming-Sheng Teng |
| collection | DOAJ |
| description | Abstract Background Hepatic lipase (HL, encoded by LIPC) is a glycoprotein primarily synthesized and secreted by hepatocytes. Previous studies had demonstrated that HL is crucial for reverse cholesterol transport and affects the metabolism, composition, and level of several lipoproteins. In current study, we investigated the association of LIPC (Lipase C, Hepatic Type) variants with circulating and urinary biomarker levels by using subgroup and mediation analyses. Methods A total of 572 participants from Taiwan were genotyped for three LIPC single nucleotide polymorphisms (SNPs) by using TaqMan assay. Fasting levels of glucose, lipid profile, inflammation markers, urine creatinine and 8-hydroxy deoxyguanosine (8-OHdG) were measured. The chi-square test, 2-sample t test and Analysis of variance (ANOVA) were used to examine differences among variables and genotype frequencies. Results SNPs rs2043085 and rs1532085 were significantly associated with urinary 8-OHdG levels, whereas all three SNPs were more significantly associated with Triglycerides (TG) or HDL-cholesterol (HDL-C) levels after additional adjustment for HDL-C or TG levels, respectively. Subgroup analyses revealed that the association of the LIPC SNPs with the levels of serum TG, HDL-C, and urinary 8-OHdG were predominantly observed in the men but not in the women. Differential associations of the LIPC SNPs with various lipid levels were observed in participants with different adiposity statuses. Mediation analyses indicated that TG levels acted as a suppressor masking the association of the LIPC genotypes with HDL-C levels, particularly in the men (Sobel test, all P < 0.01). Conclusion Our data revealed that interaction and suppression effects mediated the pleiotropic association of the LIPC variants. The effects of the LIPC SNPs depended on sex, adiposity status, and TG levels. Thus, our findings can provide a method for identifying high-risk populations of cardiovascular diseases for clinical diagnosis. |
| first_indexed | 2024-12-10T09:51:25Z |
| format | Article |
| id | doaj.art-2900a782e246447482b104b9af77d682 |
| institution | Directory Open Access Journal |
| issn | 1476-511X |
| language | English |
| last_indexed | 2024-12-10T09:51:25Z |
| publishDate | 2019-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Lipids in Health and Disease |
| spelling | doaj.art-2900a782e246447482b104b9af77d6822022-12-22T01:53:39ZengBMCLipids in Health and Disease1476-511X2019-05-0118111410.1186/s12944-019-1057-9Pleiotropic association of LIPC variants with lipid and urinary 8-hydroxy deoxyguanosine levels in a Taiwanese populationMing-Sheng Teng0Semon Wu1Lung-An Hsu2I-Shiang Tzeng3Hsin-Hua Chou4Cheng-Wen Su5Yu-Lin Ko6Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical FoundationDepartment of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical FoundationThe First Cardiovascular Division, Department of Internal Medicine, Chang Gung Memorial Hospital and Chang Gung University College of MedicineDepartment of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical FoundationThe Division of Cardiology, Department of Internal Medicine and Cardiovascular Center, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical FoundationDepartment of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical FoundationDepartment of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical FoundationAbstract Background Hepatic lipase (HL, encoded by LIPC) is a glycoprotein primarily synthesized and secreted by hepatocytes. Previous studies had demonstrated that HL is crucial for reverse cholesterol transport and affects the metabolism, composition, and level of several lipoproteins. In current study, we investigated the association of LIPC (Lipase C, Hepatic Type) variants with circulating and urinary biomarker levels by using subgroup and mediation analyses. Methods A total of 572 participants from Taiwan were genotyped for three LIPC single nucleotide polymorphisms (SNPs) by using TaqMan assay. Fasting levels of glucose, lipid profile, inflammation markers, urine creatinine and 8-hydroxy deoxyguanosine (8-OHdG) were measured. The chi-square test, 2-sample t test and Analysis of variance (ANOVA) were used to examine differences among variables and genotype frequencies. Results SNPs rs2043085 and rs1532085 were significantly associated with urinary 8-OHdG levels, whereas all three SNPs were more significantly associated with Triglycerides (TG) or HDL-cholesterol (HDL-C) levels after additional adjustment for HDL-C or TG levels, respectively. Subgroup analyses revealed that the association of the LIPC SNPs with the levels of serum TG, HDL-C, and urinary 8-OHdG were predominantly observed in the men but not in the women. Differential associations of the LIPC SNPs with various lipid levels were observed in participants with different adiposity statuses. Mediation analyses indicated that TG levels acted as a suppressor masking the association of the LIPC genotypes with HDL-C levels, particularly in the men (Sobel test, all P < 0.01). Conclusion Our data revealed that interaction and suppression effects mediated the pleiotropic association of the LIPC variants. The effects of the LIPC SNPs depended on sex, adiposity status, and TG levels. Thus, our findings can provide a method for identifying high-risk populations of cardiovascular diseases for clinical diagnosis.http://link.springer.com/article/10.1186/s12944-019-1057-9Hepatic lipaseSingle-nucleotide polymorphismMediation analysisSuppression effectTriglyceride levelHigh-density lipoprotein cholesterol level |
| spellingShingle | Ming-Sheng Teng Semon Wu Lung-An Hsu I-Shiang Tzeng Hsin-Hua Chou Cheng-Wen Su Yu-Lin Ko Pleiotropic association of LIPC variants with lipid and urinary 8-hydroxy deoxyguanosine levels in a Taiwanese population Lipids in Health and Disease Hepatic lipase Single-nucleotide polymorphism Mediation analysis Suppression effect Triglyceride level High-density lipoprotein cholesterol level |
| title | Pleiotropic association of LIPC variants with lipid and urinary 8-hydroxy deoxyguanosine levels in a Taiwanese population |
| title_full | Pleiotropic association of LIPC variants with lipid and urinary 8-hydroxy deoxyguanosine levels in a Taiwanese population |
| title_fullStr | Pleiotropic association of LIPC variants with lipid and urinary 8-hydroxy deoxyguanosine levels in a Taiwanese population |
| title_full_unstemmed | Pleiotropic association of LIPC variants with lipid and urinary 8-hydroxy deoxyguanosine levels in a Taiwanese population |
| title_short | Pleiotropic association of LIPC variants with lipid and urinary 8-hydroxy deoxyguanosine levels in a Taiwanese population |
| title_sort | pleiotropic association of lipc variants with lipid and urinary 8 hydroxy deoxyguanosine levels in a taiwanese population |
| topic | Hepatic lipase Single-nucleotide polymorphism Mediation analysis Suppression effect Triglyceride level High-density lipoprotein cholesterol level |
| url | http://link.springer.com/article/10.1186/s12944-019-1057-9 |
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