演題

Heterozygous Familial Hypercholesterolemia: Insight into Polygenetic Abnormalities in Japanese Patients

[演者] Haruki Sekiguchi:1
[共同演者] Takuro Abe:1, Eri Yamamoto:1, Noriko Kikuchi:1, Makiko Kimura:1, Akiko Sakai:1, Kayoko Sato:1, Nobuhisa Hagiwara:1
1:Department of Cardiology, Tokyo Women's Medical University, Tokyo

Background:Heterozygous familial hypercholesterolemia(heFH) is one of the most common genetic disease and the leading cause of premature cardiovascular disease(CVD). HeFH is caused by mutations in FH genes, such as those encoding LDL-receptor(LDLR),apolipoprotein B-100(APOB),proprotein convertase subtilisin/kexin type 9(PSCK9),or low-density lipoprotein receptor adapter protein 1(LDLRAP1). Recently, it was found that adenosine triphosphate-binding cassette transporter G5/8(ABCG5/8) and APOA5 are associated with CVD in Japanese hFH patients. However,the relationship between these genes and heFH is not clear. Here, we investigated the prevalence of polygenetic mutations in patients with heFH and their concurrent risk of CVD.Methods:The genotypes of 92 patients with clinical FH and probable FH according to FH guidelines of Japanese Atherosclerosis Society were analyzed using an Illumina MiSeq sequencer.Results:Gene mutations were observed in 36 of 54 patients(66.7%) with clinical FH, and 19 of 36 patients (52.8%) with probable FH. Mutations in LDLR, PSCK9, APOB, LDLRAP1, ABCG5, ABCG8, and APOA5 were seen in 9.8,19.5,4.4,4.4,22.8,13.0,and 37.0% cases, respectively. Patients with heFH that had ABCG5/8 mutations were more likely to have a history of CVD incidence. Interestingly, the average age of first CVD incidence in patients with APOA5 mutations was lower(59±9years) than that in patients without APOA5 mutations(65±years).Conclusions:Polygenetic mutations in ABCG5/8 or APOA5 were found in Japanese hFH patients with high CVD incidence. The genetic diagnosis of hFH is important in the prevention of CVD events.

[Keywords] gene expression / epidemiology
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