uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Polymorphisms in sh2b1 and spns1 loci are associated with triglyceride levels in a healthy population in northern Sweden
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology. (Helgi Schiöth)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology. (Helgi Schiöth)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. (Gyllensten)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology. (Helgi Schiöth)
Show others and affiliations
2012 (English)In: Journal of Genetics, ISSN 0022-1333, E-ISSN 0973-7731, Vol. 91, no 2, 237-240 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Springer, 2012. Vol. 91, no 2, 237-240 p.
Keyword [en]
Karesuando; NSPHS; SH2B1 gene; SPNS1; triglycerides; SOLAR.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-177647DOI: 10.1007/s12041-012-0167-1ISI: 000308363400017OAI: oai:DiVA.org:uu-177647DiVA: diva2:541353
Available from: 2012-07-17 Created: 2012-07-17 Last updated: 2017-12-07Bibliographically approved
In thesis
1. Evolution of Membrane Bound Proteins and their Ligands: The Melanocortin (MC) Receptor Inverse Agonists AgRP2, ASIP2, Drug/Metabolite Transporters, and SPNS1
Open this publication in new window or tab >>Evolution of Membrane Bound Proteins and their Ligands: The Melanocortin (MC) Receptor Inverse Agonists AgRP2, ASIP2, Drug/Metabolite Transporters, and SPNS1
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Integral membrane proteins play a key role hormonal and neuronal signaling. Transmembrane helix (TM) proteins form about 27% of the human proteome. Furthermore, 44% of the human drug targets are receptors, and 19% of these are seven-transmembrane domain receptors (GPCRs), which constitute 4% of the entire protein-coding genome. After receptors, solute carriers (SLCs) constitute the second largest superfamily of TM proteins. Three of the largest SLC families contain protein domains that are members of the drug/metabolite transporter clan.

We present evidence that the drug/metabolite transporter (DMT) families have evolved from a domain duplication event before the radiation of Viridiplantae in the EamA family (previously called domain unknown function 6). We present evidence that the family called fatty acid elongases are homologous to transporters, not enzymes as had previously been thought. We renamed several transporters, and introduced the new HGNC-approved nomenclature of SLC35G1 – 6.

We show the presence of AgRP and ASIP in elephant shark, a cartilaginous fish belonging to the subclass of Holocephali. However, we do not find any of these genes in lamprey or lancelet, suggesting that the MCA and MCB receptors function without antagonists in lamprey.

We report that a venom peptide in Plectreurys tristis has the same cysteine knot structure as fish AgRP2, a higher similarity than previously known. Here we suggest that the Agouti-like peptide genes were formed through classical subsequent gene duplications where the AgRP is likely to be the most ancestral, first splitting from a common ancestor to ASIP and A2. We introduce a new technique for synteny detection, sinusoidal Hough transform.

We found that the known obesity SNPs in SH2B1, rs4788102 (p=0.0023) and rs7498665 (p=0.0018) were associated with triglyceride levels in the North Swedish Population Health Study (NSPHS) cohort, consisting of 719 individuals from the Karesuando parish in northern Sweden. To account for kinship, the SH2B1 SNPs, and four SNPs in the expanded region were analyzed for association with triglyceride levels using SOLAR. We found a stronger signal (p=0.0009) for a SNP, near SH2B1, rs8045689, located in an intron of SPNS1 which is structurally similar to a sphingolipid transporter.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 49 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 789
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-177650 (URN)978-91-554-8407-1 (ISBN)
Public defence
2012-09-06, C8:305, BMC, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2012-08-15 Created: 2012-07-17 Last updated: 2013-01-22Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Authority records BETA

Västermark, ÅkeJacobsson, JosefinJohansson, ÅsaFredriksson, RobertGyllensten, UlfSchiöth, Helgi

Search in DiVA

By author/editor
Västermark, ÅkeJacobsson, JosefinJohansson, ÅsaFredriksson, RobertGyllensten, UlfSchiöth, Helgi
By organisation
Functional PharmacologyDepartment of Immunology, Genetics and Pathology
In the same journal
Journal of Genetics
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 901 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf