PMID- 30115944
OWN - NLM
STAT- MEDLINE
DCOM- 20191030
LR  - 20191030
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 8
IP  - 1
DP  - 2018 Aug 16
TI  - The polymorphism rs35767 at IGF1 locus is associated with serum urate levels.
PG  - 12255
LID - 10.1038/s41598-018-29665-3 [doi]
LID - 12255
AB  - Previous studies suggested that the IGF-1/IGF-1 receptor signaling pathway may 
      contribute to regulate uric acid levels. To confirm this hypothesis, we assessed 
      the effects of the IGF-1-raising genetic variant rs35767 on urate levels in serum 
      and urine, and we investigated IGF-1 ability to modulate the expression of 
      transporters involved in reabsorption and secretion of uric acid in the kidney. 
      The study population included 2794 adult Whites. 24-hour urinary uric acid 
      concentration was available for 229 subjects. rs35767 polymorphism was screened 
      using TaqMan genotyping assays. HEK293 (human embryonic kidney-293) cell line was 
      treated with IGF-1 (1, 5, 10, 50 nM) for 24-hours, and differences in the 
      expression of urate transporters were evaluated via Western Blot and real time 
      rtPCR. Individuals carrying the IGF-1-raising allele (rs35767 T) exhibited 
      significantly lower levels of serum urate according to both additive and 
      recessive models, after correction for gender, age, BMI, glucose tolerance, 
      glomerular filtration rate, and anti-hypertensive treatment. TT genotype carriers 
      displayed higher uricosuria than C allele carriers did, after adjusting for 
      confounders. Exposure of HEK293 cells to IGF-1 resulted in a dose-dependent 
      increase of uric acid transporters deputed to uric acid excretion (MRP4, NPT1 and 
      BCRP), and reduction of GLUT9 expression, the major mediator of uric acid 
      reabsorption, both at mRNA and protein level. We observed a significant 
      association between the functional polymorphism rs35767 near IGF1 with serum 
      urate concentrations and we provide a mechanistic explanation supporting a causal 
      role for IGF-1 in the regulation of uric acid homeostasis.
FAU - Mannino, Gaia C
AU  - Mannino GC
AUID- ORCID: 0000-0002-6341-4572
AD  - Department of Medical and Surgical Sciences, University "Magna Graecia" of 
      Catanzaro, Catanzaro, Italy.
FAU - Fuoco, Anastasia
AU  - Fuoco A
AD  - Department of Medical and Surgical Sciences, University "Magna Graecia" of 
      Catanzaro, Catanzaro, Italy.
FAU - Marini, Maria A
AU  - Marini MA
AD  - Department of Systems Medicine, University of Rome-Tor Vergata, Rome, Italy.
FAU - Spiga, Rosangela
AU  - Spiga R
AD  - Department of Medical and Surgical Sciences, University "Magna Graecia" of 
      Catanzaro, Catanzaro, Italy.
FAU - Di Fatta, Concetta
AU  - Di Fatta C
AD  - Department of Medical and Surgical Sciences, University "Magna Graecia" of 
      Catanzaro, Catanzaro, Italy.
FAU - Mancuso, Elettra
AU  - Mancuso E
AD  - Department of Medical and Surgical Sciences, University "Magna Graecia" of 
      Catanzaro, Catanzaro, Italy.
FAU - Perticone, Francesco
AU  - Perticone F
AD  - Department of Medical and Surgical Sciences, University "Magna Graecia" of 
      Catanzaro, Catanzaro, Italy.
FAU - Andreozzi, Francesco
AU  - Andreozzi F
AUID- ORCID: 0000-0001-9375-1513
AD  - Department of Medical and Surgical Sciences, University "Magna Graecia" of 
      Catanzaro, Catanzaro, Italy. andreozzif@unicz.it.
FAU - Sesti, Giorgio
AU  - Sesti G
AD  - Department of Medical and Surgical Sciences, University "Magna Graecia" of 
      Catanzaro, Catanzaro, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180816
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (IGF1 protein, human)
RN  - 0 (Organic Anion Transporters)
RN  - 0 (RNA, Messenger)
RN  - 0 (urate transporter)
RN  - 268B43MJ25 (Uric Acid)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
SB  - IM
MH  - Female
MH  - Gene Expression Regulation/genetics
MH  - Genetic Loci/*genetics
MH  - HEK293 Cells
MH  - Humans
MH  - Insulin-Like Growth Factor I/*genetics
MH  - Male
MH  - Middle Aged
MH  - Organic Anion Transporters/genetics
MH  - *Polymorphism, Single Nucleotide
MH  - RNA, Messenger/genetics/metabolism
MH  - Uric Acid/*blood
PMC - PMC6095867
COIS- The authors declare no competing interests.
EDAT- 2018/08/18 06:00
MHDA- 2019/10/31 06:00
PMCR- 2018/08/16
CRDT- 2018/08/18 06:00
PHST- 2018/03/19 00:00 [received]
PHST- 2018/07/12 00:00 [accepted]
PHST- 2018/08/18 06:00 [entrez]
PHST- 2018/08/18 06:00 [pubmed]
PHST- 2019/10/31 06:00 [medline]
PHST- 2018/08/16 00:00 [pmc-release]
AID - 10.1038/s41598-018-29665-3 [pii]
AID - 29665 [pii]
AID - 10.1038/s41598-018-29665-3 [doi]
PST - epublish
SO  - Sci Rep. 2018 Aug 16;8(1):12255. doi: 10.1038/s41598-018-29665-3.