Genetic association of lipid and lipid-lowing drug targets with uterine fibroids
Objective: Observational studies suggest that blood lipids are a risk factor for uterine fibroids (UFs) and that lipid-lowering drugs are beneficial for the treatment and prevention of UF; however, the conclusions are inconsistent. We aimed to determine the causal effects of lipids and lipid-lowerin...
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Elsevier
2025-01-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024175706 |
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| author | Mei Wu Qiannan Lin Siyu Li Huiyan Wang Wenbo Zhou |
| author_facet | Mei Wu Qiannan Lin Siyu Li Huiyan Wang Wenbo Zhou |
| author_sort | Mei Wu |
| collection | DOAJ |
| description | Objective: Observational studies suggest that blood lipids are a risk factor for uterine fibroids (UFs) and that lipid-lowering drugs are beneficial for the treatment and prevention of UF; however, the conclusions are inconsistent. We aimed to determine the causal effects of lipids and lipid-lowering drugs on UFs using Mendelian randomization (MR). Methods: Genetic variants from genome-wide association studies (GWAS) of lipid traits and variants in genes encoding lipid-lowering drug targets were extracted, and two independent UF GWAS were set as the outcome. Their effects on UF risk and related traits were estimated using the inverse variance weighted method. Results: The MR analysis revealed that high density lipoprotein cholesterol (HDL-C, OR = 0.88, 95 % CI: 0.83–0.93, P = 3.58E-6) and triglycerides (TG, OR = 1.14, 95 % CI: 1.07–1.21, P = 6.83E-5) were protective factors and risk factors for UF, respectively. Drug-targeted MR analysis results indicated that genetically predicted inhibition of cholesteryl ester transfer protein (CETP) was associated with a lower UF risk (OR = 0.95, 95 % CI: 0.92–0.98, P = 7.83E-4), as well as reduced levels or risk of other UF-associated clinical traits, including estradiol level, excessive menstruation, abdominal and pelvic pain, myomectomy, and miscarriage. Conclusions: Our study provides evidence that HDL-C and TG levels were causally associated with UF risk. Genetically proxied CETP inhibition may have a protective effect against UF, which warrants further investigation. |
| format | Article |
| id | doaj-art-d8a4ca08e9a84ec89fe147dc5127a719 |
| institution | Kabale University |
| issn | 2405-8440 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj-art-d8a4ca08e9a84ec89fe147dc5127a7192025-01-17T04:51:35ZengElsevierHeliyon2405-84402025-01-01111e41539Genetic association of lipid and lipid-lowing drug targets with uterine fibroidsMei Wu0Qiannan Lin1Siyu Li2Huiyan Wang3Wenbo Zhou4Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, 213000, ChinaChangzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, 213000, ChinaChangzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, 213000, ChinaCorresponding author. Department of Obstetrics and Gynecology, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, NO.16 Dingxiang Road, Changzhou, Jiangsu Province, 213000, China.; Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, 213000, ChinaCorresponding author. Medical Research Center, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University. NO.16 Dingxiang Road, Changzhou, Jiangsu Province, 213000, China.; Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, 213000, ChinaObjective: Observational studies suggest that blood lipids are a risk factor for uterine fibroids (UFs) and that lipid-lowering drugs are beneficial for the treatment and prevention of UF; however, the conclusions are inconsistent. We aimed to determine the causal effects of lipids and lipid-lowering drugs on UFs using Mendelian randomization (MR). Methods: Genetic variants from genome-wide association studies (GWAS) of lipid traits and variants in genes encoding lipid-lowering drug targets were extracted, and two independent UF GWAS were set as the outcome. Their effects on UF risk and related traits were estimated using the inverse variance weighted method. Results: The MR analysis revealed that high density lipoprotein cholesterol (HDL-C, OR = 0.88, 95 % CI: 0.83–0.93, P = 3.58E-6) and triglycerides (TG, OR = 1.14, 95 % CI: 1.07–1.21, P = 6.83E-5) were protective factors and risk factors for UF, respectively. Drug-targeted MR analysis results indicated that genetically predicted inhibition of cholesteryl ester transfer protein (CETP) was associated with a lower UF risk (OR = 0.95, 95 % CI: 0.92–0.98, P = 7.83E-4), as well as reduced levels or risk of other UF-associated clinical traits, including estradiol level, excessive menstruation, abdominal and pelvic pain, myomectomy, and miscarriage. Conclusions: Our study provides evidence that HDL-C and TG levels were causally associated with UF risk. Genetically proxied CETP inhibition may have a protective effect against UF, which warrants further investigation.http://www.sciencedirect.com/science/article/pii/S2405844024175706Uterine fibroidHDL-CLipidMendelian randomizationCETP |
| spellingShingle | Mei Wu Qiannan Lin Siyu Li Huiyan Wang Wenbo Zhou Genetic association of lipid and lipid-lowing drug targets with uterine fibroids Heliyon Uterine fibroid HDL-C Lipid Mendelian randomization CETP |
| title | Genetic association of lipid and lipid-lowing drug targets with uterine fibroids |
| title_full | Genetic association of lipid and lipid-lowing drug targets with uterine fibroids |
| title_fullStr | Genetic association of lipid and lipid-lowing drug targets with uterine fibroids |
| title_full_unstemmed | Genetic association of lipid and lipid-lowing drug targets with uterine fibroids |
| title_short | Genetic association of lipid and lipid-lowing drug targets with uterine fibroids |
| title_sort | genetic association of lipid and lipid lowing drug targets with uterine fibroids |
| topic | Uterine fibroid HDL-C Lipid Mendelian randomization CETP |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024175706 |
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