Prevalent Variants in the LDLR Gene Impair Responsiveness to Rosuvastatin among Family Members of Patients with Premature Myocardial Infarction
Background: Familial hypercholesterolemia (FH) is an inherited metabolic disorder characterized by high levels of low-density lipoprotein cholesterol (LDL-c) from birth. About 85% of all FH cases are caused by pathogenic variants in the LDLR gene. Individuals with FH have increased cardiovascular ri...
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MDPI AG
2023-12-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/13/12/1725 |
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| author | Nguyen Trung Kien Tran Tin Nghia Nguyen Minh Hoang Tran Nguyen Trong Phu Pham Thi Ngoc Nga Ha Thi Thao Mai J. Luis Espinoza |
| author_facet | Nguyen Trung Kien Tran Tin Nghia Nguyen Minh Hoang Tran Nguyen Trong Phu Pham Thi Ngoc Nga Ha Thi Thao Mai J. Luis Espinoza |
| author_sort | Nguyen Trung Kien |
| collection | DOAJ |
| description | Background: Familial hypercholesterolemia (FH) is an inherited metabolic disorder characterized by high levels of low-density lipoprotein cholesterol (LDL-c) from birth. About 85% of all FH cases are caused by pathogenic variants in the LDLR gene. Individuals with FH have increased cardiovascular risk, including a high risk of premature myocardial infarction (PMI). Methods: We conducted an opportunistic exome screening to identify variants in the LDLR gene among Vietnamese patients with PMI treated at a general hospital in southern Vietnam. A cascade testing for LDLR variants was conducted in their relatives within three generations, and the effects of the LDLR variant on the response to rosuvastatin treatment were also studied using a comparative before-and-after study design on those who were eligible. Results: A total of 99 participants from the three generations of four PMI patients were recruited, mean age 37.3 ± 18.5 years, 56.6% males. Sanger sequencing revealed two variants in the LDLR gene: variant rs577934998 (c.664T>C), detected in 17 individuals within one family, and variant rs12710260 (c.1060+10G>C), found in 32 individuals (49.5%) in the other three families tested. Individuals harboring the variant c.664T>C had significantly higher baseline LDL-c and total cholesterol levels compared to those with variant c.1060+10G>C (classified as benign) or those without LDLR variants, and among the 47 patients subjected to a 3-month course of rosuvastatin therapy, those with variant c.664T>C had a significantly higher risk of not achieving the LDL-c target after the course of treatment compared to the c.1060+10G>C carriers. Conclusions: These findings provide evidence supporting the existence of pathogenic LDLR variants in Vietnamese patients with PMI and their relatives and may indicate the need for personalizing lipid-lowering therapies. Further studies are needed to delineate the extent and severity of the problem. |
| first_indexed | 2024-03-08T20:36:50Z |
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| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-08T20:36:50Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-6681798e80674d3c9fda5285a204d4082023-12-22T14:20:06ZengMDPI AGJournal of Personalized Medicine2075-44262023-12-011312172510.3390/jpm13121725Prevalent Variants in the LDLR Gene Impair Responsiveness to Rosuvastatin among Family Members of Patients with Premature Myocardial InfarctionNguyen Trung Kien0Tran Tin Nghia1Nguyen Minh Hoang2Tran Nguyen Trong Phu3Pham Thi Ngoc Nga4Ha Thi Thao Mai5J. Luis Espinoza6Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho 900000, VietnamFaculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho 900000, VietnamTra Vinh General Hospital, Tra Vinh 940000, VietnamFaculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho 900000, VietnamFaculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho 900000, VietnamFaculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho 900000, VietnamFaculty of Health Sciences, Kanazawa University, Kanazawa 920-0942, Ishikawa, JapanBackground: Familial hypercholesterolemia (FH) is an inherited metabolic disorder characterized by high levels of low-density lipoprotein cholesterol (LDL-c) from birth. About 85% of all FH cases are caused by pathogenic variants in the LDLR gene. Individuals with FH have increased cardiovascular risk, including a high risk of premature myocardial infarction (PMI). Methods: We conducted an opportunistic exome screening to identify variants in the LDLR gene among Vietnamese patients with PMI treated at a general hospital in southern Vietnam. A cascade testing for LDLR variants was conducted in their relatives within three generations, and the effects of the LDLR variant on the response to rosuvastatin treatment were also studied using a comparative before-and-after study design on those who were eligible. Results: A total of 99 participants from the three generations of four PMI patients were recruited, mean age 37.3 ± 18.5 years, 56.6% males. Sanger sequencing revealed two variants in the LDLR gene: variant rs577934998 (c.664T>C), detected in 17 individuals within one family, and variant rs12710260 (c.1060+10G>C), found in 32 individuals (49.5%) in the other three families tested. Individuals harboring the variant c.664T>C had significantly higher baseline LDL-c and total cholesterol levels compared to those with variant c.1060+10G>C (classified as benign) or those without LDLR variants, and among the 47 patients subjected to a 3-month course of rosuvastatin therapy, those with variant c.664T>C had a significantly higher risk of not achieving the LDL-c target after the course of treatment compared to the c.1060+10G>C carriers. Conclusions: These findings provide evidence supporting the existence of pathogenic LDLR variants in Vietnamese patients with PMI and their relatives and may indicate the need for personalizing lipid-lowering therapies. Further studies are needed to delineate the extent and severity of the problem.https://www.mdpi.com/2075-4426/13/12/1725LDLR gene variantfamilial hypercholesterolemiarosuvastatinpremature acute myocardial infarctiongenetic metabolic disease |
| spellingShingle | Nguyen Trung Kien Tran Tin Nghia Nguyen Minh Hoang Tran Nguyen Trong Phu Pham Thi Ngoc Nga Ha Thi Thao Mai J. Luis Espinoza Prevalent Variants in the LDLR Gene Impair Responsiveness to Rosuvastatin among Family Members of Patients with Premature Myocardial Infarction Journal of Personalized Medicine LDLR gene variant familial hypercholesterolemia rosuvastatin premature acute myocardial infarction genetic metabolic disease |
| title | Prevalent Variants in the LDLR Gene Impair Responsiveness to Rosuvastatin among Family Members of Patients with Premature Myocardial Infarction |
| title_full | Prevalent Variants in the LDLR Gene Impair Responsiveness to Rosuvastatin among Family Members of Patients with Premature Myocardial Infarction |
| title_fullStr | Prevalent Variants in the LDLR Gene Impair Responsiveness to Rosuvastatin among Family Members of Patients with Premature Myocardial Infarction |
| title_full_unstemmed | Prevalent Variants in the LDLR Gene Impair Responsiveness to Rosuvastatin among Family Members of Patients with Premature Myocardial Infarction |
| title_short | Prevalent Variants in the LDLR Gene Impair Responsiveness to Rosuvastatin among Family Members of Patients with Premature Myocardial Infarction |
| title_sort | prevalent variants in the ldlr gene impair responsiveness to rosuvastatin among family members of patients with premature myocardial infarction |
| topic | LDLR gene variant familial hypercholesterolemia rosuvastatin premature acute myocardial infarction genetic metabolic disease |
| url | https://www.mdpi.com/2075-4426/13/12/1725 |
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