Journal of clinical lipidology · 2026
Vitamin K1 as a screening marker to facilitate the genetic diagnosis of class I familial hypobetalipoproteinemia: A prospective cohort study with a systematic review analysis.
СтатьяСистематический обзорПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Tanaka Masaki, Okazaki Sachiko, Takahashi Manabu, Wakabayashi Tetsuji, Takase Satoru, Ishiura Hiroyuki, Mitsui Jun, Tsuji Shoji, Yanagimoto Shintaro, Yamauchi Toshimasa, Okazaki Hiroaki
Аннотация
BACKGROUND: While low levels of LDL-cholesterol can be atheroprotective, homozygous Class I familial hypobetalipoproteinemia (Ho-Class I FHBL) and heterozygous Class I FHBL (He-Class I FHBL) due to APOB variants (i.e., heterozygous FHBL1 (HeFHBL1)) have serious complications due to genetic defects in the chylomicron/VLDL secretion pathway. However, Ho-Class I FHBL with milder phenotypes and HeFHBL1 are often underdiagnosed due to overlapping lipid profiles with other forms of hypobetalipoproteinemia.
OBJECTIVE: Additional screening markers are warranted.
METHODS: We established a prospective HBL cohort and performed detailed genotype-phenotype analyses to identify biomarkers associated with Class I FHBL. For further exploration, we systematically reviewed cases with Class I FHBL.
RESULTS: In our lipid genome cohort (n = 440), whole-exome sequencing of 18 consecutive cases of HBL (LDL-C <30 mg/dL) identified 7 novel pathogenic variants in 7 cases of Class I FHBL. Genotype-phenotype analyses revealed that plasma vitamin K1 is the strongest independent predictor of Class I FHBL. The vitamin K1 levels in HeFHBL1 were significantly reduced by approximately 50% compared to controls, reflecting the half-normal lipoprotein secretion. Systematic review analyses (n = 472) revealed that vitamin K1 is the only fat-soluble vitamin that is significantly decreased not only in Ho-Class I FHBL but also in HeFHBL1.
CONCLUSION: Plasma vitamin K1 may serve as a sensitive screening marker of fat malabsorption, facilitating the genetic diagnosis of Class I FHBL, enabling early management of its complications, such as fat malabsorption, fat-soluble vitamin deficiency, potential vitamin K deficiency, and steatotic liver disease.
OBJECTIVE: Additional screening markers are warranted.
METHODS: We established a prospective HBL cohort and performed detailed genotype-phenotype analyses to identify biomarkers associated with Class I FHBL. For further exploration, we systematically reviewed cases with Class I FHBL.
RESULTS: In our lipid genome cohort (n = 440), whole-exome sequencing of 18 consecutive cases of HBL (LDL-C <30 mg/dL) identified 7 novel pathogenic variants in 7 cases of Class I FHBL. Genotype-phenotype analyses revealed that plasma vitamin K1 is the strongest independent predictor of Class I FHBL. The vitamin K1 levels in HeFHBL1 were significantly reduced by approximately 50% compared to controls, reflecting the half-normal lipoprotein secretion. Systematic review analyses (n = 472) revealed that vitamin K1 is the only fat-soluble vitamin that is significantly decreased not only in Ho-Class I FHBL but also in HeFHBL1.
CONCLUSION: Plasma vitamin K1 may serve as a sensitive screening marker of fat malabsorption, facilitating the genetic diagnosis of Class I FHBL, enabling early management of its complications, such as fat malabsorption, fat-soluble vitamin deficiency, potential vitamin K deficiency, and steatotic liver disease.