論文

査読有り
2019年8月23日

Rare and Deleterious Mutations in ABCG5/ABCG8 Genes Contribute to Mimicking and Worsening of Familial Hypercholesterolemia Phenotype.

Circulation journal : official journal of the Japanese Circulation Society
  • Hayato Tada
  • ,
  • Hirofumi Okada
  • ,
  • Akihiro Nomura
  • ,
  • Satoshi Yashiro
  • ,
  • Atsushi Nohara
  • ,
  • Yasushi Ishigaki
  • ,
  • Masayuki Takamura
  • ,
  • Masa-Aki Kawashiri

83
9
開始ページ
1917
終了ページ
1924
記述言語
英語
掲載種別
DOI
10.1253/circj.CJ-19-0317

BACKGROUND: A substantial proportion of patients clinically diagnosed as having familial hypercholesterolemia (FH) do not manifest causative mutation(s) in the FH genes such asLDLR,APOB, andPCSK9. We aimed to evaluate the effect of rare and deleterious mutation(s) inABCG5/ABCG8on hyper-low-density lipoprotein (LDL) cholesterolemia in individuals who meet the clinical criteria for FH.Methods and Results:We compared the LDL cholesterol (LDL-C) values among 487 subjects with FH; the subjects were grouped according to the presence of mutation(s) in FH andABCG5/ABCG8genes. We identified 276 individuals with a deleterious mutation in 1 FH gene (57%, monogenic FH), but found no causative mutations in 156 individuals (32%, mutation-negative). A total of 37 individuals had deleterious mutations inABCG5orABCG8, but not in FH genes (8%,ABCG5/ABCG8mutation carriers). Among these, 3 individuals had sitosterolemia (0.6%) with double mutations. We also identified 18 individuals with deleterious mutations in an FH gene andABCG5orABCG8(4%,ABCG5/ABCG8-oligogenic FH). Subjects without mutations had significantly higher polygenic scores than those in any other groups. LDL-C levels in oligogenic FH subjects were significantly higher than in the monogenic FH subjects. Moreover, sitosterol/lathosterol levels were significantly affected by those mutations. CONCLUSIONS: The results suggested that rare and deleterious mutations inABCG5/ABCG8contribute substantially to mimicking and exacerbation of the FH phenotype.

リンク情報
DOI
https://doi.org/10.1253/circj.CJ-19-0317
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31327807