坂井 晶子
   Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine
   Position   Assistant Professor
Language English
Title Polygenetic Abnormalities in Japanese Patients With Heterozygous Familial Hypercholesterolemia
Conference ACC.18 (67th Annual Scientific Session & Expo)
Promoters American College of Cardiology
Conference Type International society and overseas society
Presentation Type Poster notice
Lecture Type General
Publisher and common publisherSEKIGUCHI Haruki, ◎KOIKE Toshiharu, ABE Takuro, SAKAI Akiko, SATO Kayoko, HAGIWARA Nobuhisa
Date 2018/03/10
Venue
(city and name of the country)
Orlando, USA
Society abstract Journal of the American College of Cardiolog 71(11),Supplement A1756 2018
Summary Background: Heterozygous familial hypercholesterolemia (hFH) is the most common genetic disease and leading cause of premature cardiovascular disease (CVD). However, its diagnosis rate in Japan is less than 1%. hFH is caused by mutations of FH genes such as LDLreceptor (LDLR), apolipoprotein B-100 (APOB), proprotein convertase subtilisin / kexin type 9 (PSCK9), or low-density lipoprotein receptor adapter protein 1 (LDLRAP1). Recently, adenosine triphosphate-binding cassette transporterG5/8 (ABCG5/8) and APOA5 caused of CVD in Japanese patients with hFH. However, the relationship between these gene and hFH is not clear. Here, we investigated the prevalence of polygenetic mutations in patients with hFH and their concurrent risk of CVD.

Methods: he genotypes of 92 patients (57±12 years, male 76%) with high LDL-C levels (>140 mg/d) were analyzed using an Illumina Miseq sequencer; 28 patients were diagnosed with definite hFH by the FH clinical guideline, whereas 17 were probable.

Results: Twenty-one patients were diagnosed with hFH by gene analysis and 77.8% had gene mutations. The LDLR mutation was observed in 20.0%; APOB,4.4%; PSCK9,26.7%; LDLRAP1,4.4%; ABCG5,17.8%; ABCG8,6.7%; APOA5,22.2%. Patients with hFH that also had ABCG5/8 mutations were more likely to have a history of CVD incidence than were patients without these mutations (63% vs 47%). Sixty-seven percent of patients with the APOA5 mutation and 56% of those without the mutation also had a history of CVD incidence. Interestingly, the average age of first CVD incidence in patients with APOA5 mutations was the lower(33±2 years) compared without APOA5

Conclusion: Japanese patients with hFH could have concurrent genetic mutations in ABCG5/8 or APOA5, placing them at higher risk of CVD incidence. The genetic diagnosis of hFH is important for hFH patient and their descendant to prevent CVD incidence.