Genetic Testing Enables the Diagnosis of Familial Hypercholesterolemia Underdiagnosed by Clinical Criteria: Analysis of Japanese Early-Onset Coronary Artery Disease Patients
Definitive diagnosis of familial hypercholesterolemia (FH) is paramount for the risk management of patients and their relatives. The present study aimed to investigate the frequency of gene variants contributing to low-density lipoprotein cholesterol (LDL-C) metabolism and their clinical relevance i...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Hindawi Limited
2023-01-01
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| Series: | Cardiology Research and Practice |
| Online Access: | http://dx.doi.org/10.1155/2023/2236422 |
| _version_ | 1797832752540680192 |
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| author | Hiroshi Miyama Yoshinori Katsumata Mizuki Momoi Genki Ichihara Taishi Fujisawa Jin Endo Takashi Kawakami Masaharu Kataoka Shinsuke Yuasa Motoaki Sano Kazuki Sato Keiichi Fukuda |
| author_facet | Hiroshi Miyama Yoshinori Katsumata Mizuki Momoi Genki Ichihara Taishi Fujisawa Jin Endo Takashi Kawakami Masaharu Kataoka Shinsuke Yuasa Motoaki Sano Kazuki Sato Keiichi Fukuda |
| author_sort | Hiroshi Miyama |
| collection | DOAJ |
| description | Definitive diagnosis of familial hypercholesterolemia (FH) is paramount for the risk management of patients and their relatives. The present study aimed to investigate the frequency of gene variants contributing to low-density lipoprotein cholesterol (LDL-C) metabolism and their clinical relevance in patients with early-onset coronary artery disease (EOCAD). Among 63 consecutive patients with EOCAD (men <55 years or women <65 years) who underwent percutaneous coronary intervention (PCI) from 2013 to 2019 at Keio University Hospital, 52 consented to participate in this retrospective study. Targeted sequencing of LDLR, PCSK9, APOB, and LDLRAP1 was performed. Of the 52 patients enrolled (42 men; mean age: 50 ± 6 years), one (LDLR, c.1221_1222delCGinsT) harbored a pathogenic mutation, and one (APOB, c.10591A>G) harbored variants of uncertain significance. Both the patients harboring the variants were male, showing no history of diabetes mellitus or chronic kidney disease, no family history of EOCAD, and no physical findings of FH (i.e., tendon xanthomas or Achilles tendon thickening). Patients harboring the LDLR variant had three-vessel disease, were on a statin prescription at baseline, and had stable LDL-C levels; however, the case showed a poor response to the intensification of medication after PCI. Approximately 3.8% of patients with EOCAD harbored variants of gene related to LDL-C metabolism; there were no notable indicators in the patients’ background or clinical course to diagnose FH. Given the difficulty in diagnosing FH based on clinical manifestations and family history, genetic testing could enable the identification of hidden risk factors and provide early warnings to their relatives. |
| first_indexed | 2024-04-09T14:13:55Z |
| format | Article |
| id | doaj.art-3c5746adb01243cc96b7125bb40211b2 |
| institution | Directory Open Access Journal |
| issn | 2090-0597 |
| language | English |
| last_indexed | 2024-04-09T14:13:55Z |
| publishDate | 2023-01-01 |
| publisher | Hindawi Limited |
| record_format | Article |
| series | Cardiology Research and Practice |
| spelling | doaj.art-3c5746adb01243cc96b7125bb40211b22023-05-06T00:00:18ZengHindawi LimitedCardiology Research and Practice2090-05972023-01-01202310.1155/2023/2236422Genetic Testing Enables the Diagnosis of Familial Hypercholesterolemia Underdiagnosed by Clinical Criteria: Analysis of Japanese Early-Onset Coronary Artery Disease PatientsHiroshi Miyama0Yoshinori Katsumata1Mizuki Momoi2Genki Ichihara3Taishi Fujisawa4Jin Endo5Takashi Kawakami6Masaharu Kataoka7Shinsuke Yuasa8Motoaki Sano9Kazuki Sato10Keiichi Fukuda11Department of CardiologyDepartment of CardiologyDepartment of CardiologyDepartment of CardiologyDepartment of CardiologyDepartment of CardiologyDepartment of CardiologyDepartment of CardiologyDepartment of CardiologyDepartment of CardiologyInstitute for Integrated Sports MedicineDepartment of CardiologyDefinitive diagnosis of familial hypercholesterolemia (FH) is paramount for the risk management of patients and their relatives. The present study aimed to investigate the frequency of gene variants contributing to low-density lipoprotein cholesterol (LDL-C) metabolism and their clinical relevance in patients with early-onset coronary artery disease (EOCAD). Among 63 consecutive patients with EOCAD (men <55 years or women <65 years) who underwent percutaneous coronary intervention (PCI) from 2013 to 2019 at Keio University Hospital, 52 consented to participate in this retrospective study. Targeted sequencing of LDLR, PCSK9, APOB, and LDLRAP1 was performed. Of the 52 patients enrolled (42 men; mean age: 50 ± 6 years), one (LDLR, c.1221_1222delCGinsT) harbored a pathogenic mutation, and one (APOB, c.10591A>G) harbored variants of uncertain significance. Both the patients harboring the variants were male, showing no history of diabetes mellitus or chronic kidney disease, no family history of EOCAD, and no physical findings of FH (i.e., tendon xanthomas or Achilles tendon thickening). Patients harboring the LDLR variant had three-vessel disease, were on a statin prescription at baseline, and had stable LDL-C levels; however, the case showed a poor response to the intensification of medication after PCI. Approximately 3.8% of patients with EOCAD harbored variants of gene related to LDL-C metabolism; there were no notable indicators in the patients’ background or clinical course to diagnose FH. Given the difficulty in diagnosing FH based on clinical manifestations and family history, genetic testing could enable the identification of hidden risk factors and provide early warnings to their relatives.http://dx.doi.org/10.1155/2023/2236422 |
| spellingShingle | Hiroshi Miyama Yoshinori Katsumata Mizuki Momoi Genki Ichihara Taishi Fujisawa Jin Endo Takashi Kawakami Masaharu Kataoka Shinsuke Yuasa Motoaki Sano Kazuki Sato Keiichi Fukuda Genetic Testing Enables the Diagnosis of Familial Hypercholesterolemia Underdiagnosed by Clinical Criteria: Analysis of Japanese Early-Onset Coronary Artery Disease Patients Cardiology Research and Practice |
| title | Genetic Testing Enables the Diagnosis of Familial Hypercholesterolemia Underdiagnosed by Clinical Criteria: Analysis of Japanese Early-Onset Coronary Artery Disease Patients |
| title_full | Genetic Testing Enables the Diagnosis of Familial Hypercholesterolemia Underdiagnosed by Clinical Criteria: Analysis of Japanese Early-Onset Coronary Artery Disease Patients |
| title_fullStr | Genetic Testing Enables the Diagnosis of Familial Hypercholesterolemia Underdiagnosed by Clinical Criteria: Analysis of Japanese Early-Onset Coronary Artery Disease Patients |
| title_full_unstemmed | Genetic Testing Enables the Diagnosis of Familial Hypercholesterolemia Underdiagnosed by Clinical Criteria: Analysis of Japanese Early-Onset Coronary Artery Disease Patients |
| title_short | Genetic Testing Enables the Diagnosis of Familial Hypercholesterolemia Underdiagnosed by Clinical Criteria: Analysis of Japanese Early-Onset Coronary Artery Disease Patients |
| title_sort | genetic testing enables the diagnosis of familial hypercholesterolemia underdiagnosed by clinical criteria analysis of japanese early onset coronary artery disease patients |
| url | http://dx.doi.org/10.1155/2023/2236422 |
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