セキグチ　ハルキ   SEKIGUCHI Haruki   関口　治樹    所属   医学部 医学科（東京女子医科大学病院）    職種   准教授
言語種別	英語
発表タイトル	Polygenetic Abnormalities in Japanese Patients With Heterozygous Familial Hypercholesterolemia
会議名	ACC.18 (67th Annual Scientific Session & Expo)
主催者	American College of Cardiology
学会区分	国際学会及び海外の学会
発表形式	ポスター掲示
講演区分	一般
発表者・共同発表者	SEKIGUCHI Haruki, ◎KOIKE Toshiharu, ABE Takuro, SAKAI Akiko, SATO Kayoko, HAGIWARA Nobuhisa
発表年月日	2018/03/10
開催地 （都市, 国名）	Orlando, USA
学会抄録	Journal of the American College of Cardiolog 71(11),Supplement A1756 2018
概要	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.