Limits...
Half a Century Tales of Familial Hypercholesterolemia (FH) in Japan

View Article: PubMed Central - PubMed

ABSTRACT

Familial hypercholesterolemia (FH) is a disease characterized by a triad: elevated low-density lipoprotein (LDL) cholesterol, tendon xanthomas, and premature coronary heart disease. Thus, it can be considered as a model disease for hypercholesterolemia and atherosclerotic cardiovascular disease (ASCVD). For the diagnosis of hetero-FH, the detection of Achilles tendon xanthomas by palpation or on X-ray is an indispensable diagnostic skill in clinical lipidology. To prevent the under-diagnosis and under-treatment of FH, the diagnostic criteria should be more convenient and user-friendly. For a patient with cutaneous or tendon xanthomas, the probability of FH is very high; however, an absence of xanthoma does not rule out FH.

Brown and Goldstein elucidated the pathogenesis of FH by their work on LDL-receptor (LDL-R), for which they were awarded the Nobel Prize in 1985. In the 1950s, FH patients were divided into heterozygous (hetero-) and homozygous (homo-) FH, and diagnosing homo- and hetero-FH based on the phenotypic features of ASCVD or xanthomas frequently became difficult without the DNA analysis of FH genes. It is estimated that heterozygous mutations in the LDL-R or the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene will be found at a combined frequency of 0.005, which corresponds to 1/199 people in the general population in Japan.

Statins and anti-PCSK9 monoclonal antibodies are highly specific and efficient drugs for treating hetero- or homo-FH patients. Most clinical studies have reported an amelioration of ASCVD using long-term statin therapy. Clinical results using anti-PCSK9 monoclonal antibodies will emerge in a few years. In homo-FH patients, mipomersen and lomitapide are expected to yield good results. It is important to sequentially unravel the unrecognized pathogenetic mechanisms of FH to reduce its under-recognition and develop new management strategies for it.

No MeSH data available.


The frequency of FH gene mutations in LDL-receptor and PCSK9 in Japan.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5383536&req=5

Figure 9: The frequency of FH gene mutations in LDL-receptor and PCSK9 in Japan.

Mentions: FH caused by autosomal recessive hypercholesterolemia (ARH)13, 14) and signal-transducing adaptor family member 1 abnormality15) has also been reported. Similarly, the discovery of several other genes causing FH is anticipated. The frequencies of abnormalities in the FH-related genes identified till date in our laboratory are presented in Table 1 and Figs. 8 and 9.


Half a Century Tales of Familial Hypercholesterolemia (FH) in Japan
The frequency of FH gene mutations in LDL-receptor and PCSK9 in Japan.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5383536&req=5

Figure 9: The frequency of FH gene mutations in LDL-receptor and PCSK9 in Japan.
Mentions: FH caused by autosomal recessive hypercholesterolemia (ARH)13, 14) and signal-transducing adaptor family member 1 abnormality15) has also been reported. Similarly, the discovery of several other genes causing FH is anticipated. The frequencies of abnormalities in the FH-related genes identified till date in our laboratory are presented in Table 1 and Figs. 8 and 9.

View Article: PubMed Central - PubMed

ABSTRACT

Familial hypercholesterolemia (FH) is a disease characterized by a triad: elevated low-density lipoprotein (LDL) cholesterol, tendon xanthomas, and premature coronary heart disease. Thus, it can be considered as a model disease for hypercholesterolemia and atherosclerotic cardiovascular disease (ASCVD). For the diagnosis of hetero-FH, the detection of Achilles tendon xanthomas by palpation or on X-ray is an indispensable diagnostic skill in clinical lipidology. To prevent the under-diagnosis and under-treatment of FH, the diagnostic criteria should be more convenient and user-friendly. For a patient with cutaneous or tendon xanthomas, the probability of FH is very high; however, an absence of xanthoma does not rule out FH.

Brown and Goldstein elucidated the pathogenesis of FH by their work on LDL-receptor (LDL-R), for which they were awarded the Nobel Prize in 1985. In the 1950s, FH patients were divided into heterozygous (hetero-) and homozygous (homo-) FH, and diagnosing homo- and hetero-FH based on the phenotypic features of ASCVD or xanthomas frequently became difficult without the DNA analysis of FH genes. It is estimated that heterozygous mutations in the LDL-R or the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene will be found at a combined frequency of 0.005, which corresponds to 1/199 people in the general population in Japan.

Statins and anti-PCSK9 monoclonal antibodies are highly specific and efficient drugs for treating hetero- or homo-FH patients. Most clinical studies have reported an amelioration of ASCVD using long-term statin therapy. Clinical results using anti-PCSK9 monoclonal antibodies will emerge in a few years. In homo-FH patients, mipomersen and lomitapide are expected to yield good results. It is important to sequentially unravel the unrecognized pathogenetic mechanisms of FH to reduce its under-recognition and develop new management strategies for it.

No MeSH data available.