PMID- 37841863
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240210
DP  - 2023 Sep 28
TI  - The impact of blood MCP-1 levels on Alzheimer's disease with genetic variation of 
      UNC5C and NAV3 loci.
LID - rs.3.rs-3376348 [pii]
LID - 10.21203/rs.3.rs-3376348/v1 [doi]
AB  - BACKGROUND: Previous study shows that monocyte chemoattractant protein-1 (MCP-1), 
      which is implicated in the peripheral proinflammatory cascade and blood-brain 
      barrier (BBB) disruption, modulates the genetic risks of AD in established AD 
      loci. METHODS: In this study, we hypothesized that blood MCP-1 impacts the AD 
      risk of genetic variants beyond known AD loci. We thus performed a genome-wide 
      association study (GWAS) using the logistic regression via generalized estimating 
      equations (GEE) and the Cox proportional-hazards models to examine the 
      interactive effects between single nucleotide polymorphisms (SNPs) and blood 
      MCP-1 level on AD in three cohorts: the Framingham Heart Study (FHS), Alzheimer's 
      Disease Neuroimaging Initiative (ADNI) and Religious Orders Study/Memory and 
      Aging Project (ROSMAP). RESULTS: We identified SNPs in two genes, neuron 
      navigator 3 (NAV3, also named Unc-53 Homolog 3, rs696468) (p < 7.55x10(- 9)) and 
      Unc-5 Netrin Receptor C (UNC5C rs72659964) (p < 1.07x10(- 8)) that showed an 
      association between increasing levels of blood MCP-1 and AD. Elevating blood 
      MCP-1 concentrations increased AD risk and AD pathology in genotypes of NAV3 
      (rs696468-CC) and UNC5C (rs72659964-AT + TT), but did not influence the other 
      counterpart genotypes of these variants. CONCLUSIONS: NAV3 and UNC5C are homologs 
      and may increase AD risk through dysregulating the functions of neurite outgrowth 
      and guidance. Overall, the association of risk alleles of NAV3 and UNC5C with AD 
      is enhanced by peripheral MCP-1 level, suggesting that lowering the level of 
      blood MCP-1 may reduce the risk of developing AD for people with these genotypes.
FAU - Huang, Jinghan
AU  - Huang J
AD  - Boston University Chobanian & Avedisian School of Medicine.
FAU - Wang, Yixuan
AU  - Wang Y
AD  - Boston University Chobanian & Avedisian School of Medicine.
FAU - Stein, Thor D
AU  - Stein TD
AD  - Boston University Chobanian & Avedisian School of Medicine.
FAU - Ang, Ting Fang Alvin
AU  - Ang TFA
AD  - Boston University Chobanian & Avedisian School of Medicine.
FAU - Zhu, Yibo
AU  - Zhu Y
AD  - Boston University Chobanian & Avedisian School of Medicine.
FAU - Tao, Qiushan
AU  - Tao Q
AD  - Boston University Chobanian & Avedisian School of Medicine.
FAU - Lunetta, Kathryn L
AU  - Lunetta KL
AD  - Boston University School of Public Health.
FAU - Mez, Jesse
AU  - Mez J
AD  - Boston University Chobanian & Avedisian School of Medicine.
FAU - Au, Rhoda
AU  - Au R
AD  - Boston University Chobanian & Avedisian School of Medicine.
FAU - Farrer, Lindsay A
AU  - Farrer LA
AD  - Boston University Chobanian & Avedisian School of Medicine.
FAU - Qiu, Wei Qiao
AU  - Qiu WQ
AD  - Boston University Chobanian & Avedisian School of Medicine.
FAU - Zhang, Xiaoling
AU  - Zhang X
AD  - Boston University Chobanian & Avedisian School of Medicine.
LA  - eng
GR  - U01 AG046152/AG/NIA NIH HHS/United States
GR  - R01 AG017917/AG/NIA NIH HHS/United States
GR  - RC2 AG036547/AG/NIA NIH HHS/United States
GR  - R01 AG048015/AG/NIA NIH HHS/United States
GR  - U01 AG061356/AG/NIA NIH HHS/United States
GR  - U01 AG032984/AG/NIA NIH HHS/United States
GR  - R01 AG030146/AG/NIA NIH HHS/United States
GR  - U01 AG024904/AG/NIA NIH HHS/United States
GR  - R01 AG036042/AG/NIA NIH HHS/United States
GR  - P30 AG010161/AG/NIA NIH HHS/United States
GR  - R01 AG048927/AG/NIA NIH HHS/United States
GR  - RF1 AG057473/AG/NIA NIH HHS/United States
GR  - RF1 AG057519/AG/NIA NIH HHS/United States
GR  - U01 AG046161/AG/NIA NIH HHS/United States
GR  - U19 AG068753/AG/NIA NIH HHS/United States
GR  - R01 AG036836/AG/NIA NIH HHS/United States
GR  - R01 AG015819/AG/NIA NIH HHS/United States
PT  - Preprint
DEP - 20230928
PL  - United States
TA  - Res Sq
JT  - Research square
JID - 101768035
PMC - PMC10571626
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - MCP-1
OT  - blood
OT  - genome-wide association study
OT  - peripheral inflammation
COIS- Competing interests The authors declare that they have no competing interests.
EDAT- 2023/10/16 06:48
MHDA- 2023/10/16 06:49
PMCR- 2023/10/13
CRDT- 2023/10/16 04:43
PHST- 2023/10/16 06:49 [medline]
PHST- 2023/10/16 06:48 [pubmed]
PHST- 2023/10/16 04:43 [entrez]
PHST- 2023/10/13 00:00 [pmc-release]
AID - rs.3.rs-3376348 [pii]
AID - 10.21203/rs.3.rs-3376348/v1 [doi]
PST - epublish
SO  - Res Sq [Preprint]. 2023 Sep 28:rs.3.rs-3376348. doi: 10.21203/rs.3.rs-3376348/v1.