PMID- 32768567
OWN - NLM
STAT- MEDLINE
DCOM- 20210527
LR  - 20210527
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Linking)
VI  - 160
DP  - 2020 Nov 20
TI  - Telomere length and mtDNA copy number in human cystathionine beta-synthase 
      deficiency.
PG  - 219-226
LID - S0891-5849(20)31183-7 [pii]
LID - 10.1016/j.freeradbiomed.2020.07.036 [doi]
AB  - Telomere shortening and mitochondrial DNA (mtDNA) copy number are associated with 
      human disease and a reduced life span. Cystathionine beta-synthase (CBS) is a 
      housekeeping enzyme that catalyzes the first step in metabolic conversion of 
      homocysteine (Hcy) to cysteine. Mutations in the CBS gene cause CBS deficiency, a 
      rare recessive metabolic disease, manifested by severe hyperhomocysteinemia 
      (HHcy) and thromboembolism, which ultimately reduces the life span. However, it 
      was not known whether telomere shortening or mtDNA is involved in the pathology 
      of human CBS deficiency. We quantified leukocyte telomere length (TL), mtDNA copy 
      number, and plasma Hcy levels in CBS(-/)(-) patients (n = 23) and in sex- and 
      age-matched unaffected CBS(+/+) control individuals (n = 28) 0.08-57 years old. 
      We found that TL was significantly increased in severely HHcy CBS(-/)(-) female 
      patients but unaffected in severely HHcy CBS(-/)(-) male patients, relative to 
      the corresponding CBS(+/+) controls who had normal plasma Hcy levels. In multiple 
      regression analysis TL was associated with CBS genotype in women but not in men. 
      MtDNA copy number was not significantly affected by the CBS(-/)(-) genotype. 
      Taken together, these findings identify the CBS gene as a new locus in human DNA 
      that affects TL in women and illustrate a concept that a housekeeping metabolic 
      gene can be involved in telomere biology. Our findings suggest that neither 
      telomere shortening nor reduced mtDNA copy number contribute to the reduced life 
      span in CBS(-/)(-) patients.
CI  - Copyright (c) 2020. Published by Elsevier Inc.
FAU - Utyro, Olga
AU  - Utyro O
AD  - Department of Biochemistry and Biotechnology, Poznan University of Life Sciences, 
      60-632, Poznan, Poland; Institute of Bioorganic Chemistry, Polish Academy of 
      Sciences, 61-704, Poznan, Poland.
FAU - Perla-Kajan, Joanna
AU  - Perla-Kajan J
AD  - Department of Biochemistry and Biotechnology, Poznan University of Life Sciences, 
      60-632, Poznan, Poland.
FAU - Kubalska, Jolanta
AU  - Kubalska J
AD  - Department of Genetics, Institute of Psychiatry and Neurology, 02-957, Warsaw, 
      Poland.
FAU - Graban, Alla
AU  - Graban A
AD  - Department of Genetics, Institute of Psychiatry and Neurology, 02-957, Warsaw, 
      Poland.
FAU - Jakubowski, Hieronim
AU  - Jakubowski H
AD  - Department of Biochemistry and Biotechnology, Poznan University of Life Sciences, 
      60-632, Poznan, Poland; Department of Microbiology, Biochemistry and Molecular 
      Genetics, Rutgers University-New Jersey Medical School, International Center for 
      Public Health, Newark, NJ, 07103, USA. Electronic address: jakubows@rutgers.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200805
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (DNA, Mitochondrial)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - EC 4.2.1.22 (Cystathionine beta-Synthase)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Child
MH  - Child, Preschool
MH  - *Cystathionine beta-Synthase/deficiency/genetics
MH  - DNA Copy Number Variations
MH  - *DNA, Mitochondrial/genetics
MH  - Female
MH  - Homocysteine
MH  - *Homocystinuria
MH  - Humans
MH  - *Hyperhomocysteinemia
MH  - Infant
MH  - Infant, Newborn
MH  - Male
MH  - Middle Aged
MH  - Telomere/genetics
MH  - *Telomere Shortening
MH  - Young Adult
OTO - NOTNLM
OT  - Cystathionine beta-synthase deficiency
OT  - Homocysteine
OT  - Life span
OT  - Telomere dynamics
OT  - Thromboembolism
OT  - mtDNA
EDAT- 2020/08/10 06:00
MHDA- 2021/05/28 06:00
CRDT- 2020/08/10 06:00
PHST- 2020/06/18 00:00 [received]
PHST- 2020/07/24 00:00 [revised]
PHST- 2020/07/27 00:00 [accepted]
PHST- 2020/08/10 06:00 [pubmed]
PHST- 2021/05/28 06:00 [medline]
PHST- 2020/08/10 06:00 [entrez]
AID - S0891-5849(20)31183-7 [pii]
AID - 10.1016/j.freeradbiomed.2020.07.036 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2020 Nov 20;160:219-226. doi: 
      10.1016/j.freeradbiomed.2020.07.036. Epub 2020 Aug 5.