Common mutations of familial hypercholesterolemia patients in Taiwan: Characteristics and implications of migrations from southeast China

Kuan Rau Chiou, Min Ji Charng

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in low-density lipoprotein receptor (LDLR), apolipoprotein B-100 (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. This study investigated FH patients carrying common mutations in Taiwan and compared them to FH southeastern Asians. Causal FH mutations were identified by exon-by-exon sequencing with/without multiplex ligation-dependent probe amplification among 208 Taiwanese with clinically diagnosed FH. Haplotype analyses among probands and family members were undertaken using TaqMan® Assays. Totally, LDLR mutations were found in 118 probands, consisting of 61 different loci, and APOB 10579C>T mutations in 12 probands. Three mutations (64delG, 1661C>T, and 2099A>G) were novel. LDLR 986G>A (13.1%), 1747C>T (10.8%), and APOB 10579C>T (9.2%) were common mutations with no differences in phenotypes. LDLR 1747C>T associated with one haplotype (CAAGCCCCATGG/(dTA)n-112nt); LDLR 986G>A with two. APOB 10579C>T associated with the same LDLR binding-domain pattern in Taiwanese and southeastern Asians. We concluded that LDLR 986G>A, 1747C>T and APOB 10579C>T are common mutations, with combined frequency of approximately 33%. The presence of different haplotypes associated with FH common mutations in Taiwan indicates multiple historical migrations, probable multiple recurrent origins from southern China, and haplotype homologies reflect the presence of common ancestors in southern China.

Original languageEnglish
Pages (from-to)100-106
Number of pages7
JournalGene
Volume498
Issue number1
DOIs
Publication statusPublished - Apr 25 2012
Externally publishedYes

Fingerprint

Hyperlipoproteinemia Type II
Taiwan
LDL Receptors
China
Apolipoprotein B-100
Mutation
Haplotypes
Exons
Multiplex Polymerase Chain Reaction
Phenotype

Keywords

  • Chinese
  • Familial hypercholesterolemia
  • Haplotype
  • Mutation
  • Taiwanese

ASJC Scopus subject areas

  • Genetics

Cite this

Common mutations of familial hypercholesterolemia patients in Taiwan : Characteristics and implications of migrations from southeast China. / Chiou, Kuan Rau; Charng, Min Ji.

In: Gene, Vol. 498, No. 1, 25.04.2012, p. 100-106.

Research output: Contribution to journalArticle

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abstract = "Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in low-density lipoprotein receptor (LDLR), apolipoprotein B-100 (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. This study investigated FH patients carrying common mutations in Taiwan and compared them to FH southeastern Asians. Causal FH mutations were identified by exon-by-exon sequencing with/without multiplex ligation-dependent probe amplification among 208 Taiwanese with clinically diagnosed FH. Haplotype analyses among probands and family members were undertaken using TaqMan{\circledR} Assays. Totally, LDLR mutations were found in 118 probands, consisting of 61 different loci, and APOB 10579C>T mutations in 12 probands. Three mutations (64delG, 1661C>T, and 2099A>G) were novel. LDLR 986G>A (13.1{\%}), 1747C>T (10.8{\%}), and APOB 10579C>T (9.2{\%}) were common mutations with no differences in phenotypes. LDLR 1747C>T associated with one haplotype (CAAGCCCCATGG/(dTA)n-112nt); LDLR 986G>A with two. APOB 10579C>T associated with the same LDLR binding-domain pattern in Taiwanese and southeastern Asians. We concluded that LDLR 986G>A, 1747C>T and APOB 10579C>T are common mutations, with combined frequency of approximately 33{\%}. The presence of different haplotypes associated with FH common mutations in Taiwan indicates multiple historical migrations, probable multiple recurrent origins from southern China, and haplotype homologies reflect the presence of common ancestors in southern China.",
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