Abstract
Aim: The autosomal recessive hypercholesterolemia (ARH) gene is located on chromosome 1p35 and encodes a 308-amino acid protein containing a phosphotyrosine-binding domain. Several researchers have identified mutations of ARH that cause autosomal recessive hypercholesterolemia; however, it remains unknown whether this gene is involved in common hypercholesterolemia. Methods and Results: We searched for polymorphisms of the ARH gene by denaturing high-performance liquid chromatography and direct sequencing. We identified 18 single nucleotide polymorphisms of the gene, including 9 novel polymorphisms, and determined 2 haplotype blocks. No association was observed between common hypercholesterolemia and any polymorphisms or haplotypes of the ARH gene; however, we newly identified a rare Thr56Met missense mutation located in the phosphotyrosine-binding domain, which is the functional domain responsible for cholesterol metabolism. Among 1,800 Japanese individuals enrolled in the Suita study, only 4 were heterozygous for Thr56Met and all had hypercholesterolemia. The total cholesterol level and low-density lipoprotein cholesterol level of diabetic patients with the Thr56Met missense mutation was 276.3 ± 13.8 mg/dL and 185.3 ± 7.37 mg/dL, respectively. Conclusions: Because the Thr56Met missense mutation occurs in an orthologously conserved functional domain and all subjects with the mutation had hypercholesterolemia resembling familiar hypercholesterolemia, it may be a cause of familial hypercholesterolemia.
| Original language | English |
|---|---|
| Pages (from-to) | 131-140 |
| Number of pages | 10 |
| Journal | Journal of Atherosclerosis and Thrombosis |
| Volume | 17 |
| Issue number | 2 |
| Publication status | Published - 2010 |
| Externally published | Yes |
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Keywords
- Autosomal recessive hypercholesterolemia
- Mutation
- Phosphotyrosine-binding domain
- SNPs
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Internal Medicine
- Biochemistry, medical
Cite this
A novel Thr56Met mutation of the autosomal recessive hypercholesterolemia gene associated with hypercholesterolemia. / Harada, Koji; Miyamoto, Yoshihiro; Morisaki, Hiroko; Ohta, Naotaka; Yamanaka, Itaru; Kokubo, Yoshihiro; Makino, Hisashi; Harada-Shiba, Mariko; Okayama, Akira; Tomoike, Hitonobu; Okamura, Tomonori; Saito, Yoshihiko; Yoshimasa, Yasunao; Morisaki, Takayuki.
In: Journal of Atherosclerosis and Thrombosis, Vol. 17, No. 2, 2010, p. 131-140.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A novel Thr56Met mutation of the autosomal recessive hypercholesterolemia gene associated with hypercholesterolemia
AU - Harada, Koji
AU - Miyamoto, Yoshihiro
AU - Morisaki, Hiroko
AU - Ohta, Naotaka
AU - Yamanaka, Itaru
AU - Kokubo, Yoshihiro
AU - Makino, Hisashi
AU - Harada-Shiba, Mariko
AU - Okayama, Akira
AU - Tomoike, Hitonobu
AU - Okamura, Tomonori
AU - Saito, Yoshihiko
AU - Yoshimasa, Yasunao
AU - Morisaki, Takayuki
PY - 2010
Y1 - 2010
N2 - Aim: The autosomal recessive hypercholesterolemia (ARH) gene is located on chromosome 1p35 and encodes a 308-amino acid protein containing a phosphotyrosine-binding domain. Several researchers have identified mutations of ARH that cause autosomal recessive hypercholesterolemia; however, it remains unknown whether this gene is involved in common hypercholesterolemia. Methods and Results: We searched for polymorphisms of the ARH gene by denaturing high-performance liquid chromatography and direct sequencing. We identified 18 single nucleotide polymorphisms of the gene, including 9 novel polymorphisms, and determined 2 haplotype blocks. No association was observed between common hypercholesterolemia and any polymorphisms or haplotypes of the ARH gene; however, we newly identified a rare Thr56Met missense mutation located in the phosphotyrosine-binding domain, which is the functional domain responsible for cholesterol metabolism. Among 1,800 Japanese individuals enrolled in the Suita study, only 4 were heterozygous for Thr56Met and all had hypercholesterolemia. The total cholesterol level and low-density lipoprotein cholesterol level of diabetic patients with the Thr56Met missense mutation was 276.3 ± 13.8 mg/dL and 185.3 ± 7.37 mg/dL, respectively. Conclusions: Because the Thr56Met missense mutation occurs in an orthologously conserved functional domain and all subjects with the mutation had hypercholesterolemia resembling familiar hypercholesterolemia, it may be a cause of familial hypercholesterolemia.
AB - Aim: The autosomal recessive hypercholesterolemia (ARH) gene is located on chromosome 1p35 and encodes a 308-amino acid protein containing a phosphotyrosine-binding domain. Several researchers have identified mutations of ARH that cause autosomal recessive hypercholesterolemia; however, it remains unknown whether this gene is involved in common hypercholesterolemia. Methods and Results: We searched for polymorphisms of the ARH gene by denaturing high-performance liquid chromatography and direct sequencing. We identified 18 single nucleotide polymorphisms of the gene, including 9 novel polymorphisms, and determined 2 haplotype blocks. No association was observed between common hypercholesterolemia and any polymorphisms or haplotypes of the ARH gene; however, we newly identified a rare Thr56Met missense mutation located in the phosphotyrosine-binding domain, which is the functional domain responsible for cholesterol metabolism. Among 1,800 Japanese individuals enrolled in the Suita study, only 4 were heterozygous for Thr56Met and all had hypercholesterolemia. The total cholesterol level and low-density lipoprotein cholesterol level of diabetic patients with the Thr56Met missense mutation was 276.3 ± 13.8 mg/dL and 185.3 ± 7.37 mg/dL, respectively. Conclusions: Because the Thr56Met missense mutation occurs in an orthologously conserved functional domain and all subjects with the mutation had hypercholesterolemia resembling familiar hypercholesterolemia, it may be a cause of familial hypercholesterolemia.
KW - Autosomal recessive hypercholesterolemia
KW - Mutation
KW - Phosphotyrosine-binding domain
KW - SNPs
UR - http://www.scopus.com/inward/record.url?scp=77649198885&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77649198885&partnerID=8YFLogxK
M3 - Article
C2 - 20124734
AN - SCOPUS:77649198885
VL - 17
SP - 131
EP - 140
JO - Journal of Atherosclerosis and Thrombosis
JF - Journal of Atherosclerosis and Thrombosis
SN - 1340-3478
IS - 2
ER -