title: ANGPTL8/Betatrophin R59W variant is associated with higher glucose level in non-diabetic Arabs living in Kuwaits.
abstract: BACKGROUND
  ANGPTL8 (betatrophin) has been recently identified as a regulator of lipid metabolism through its interaction with ANGPTL3. A sequence variant in ANGPTL8 has been shown to associate with lower level of Low Density Lipoprotein (LDL) and High Density Lipoprotein (HDL). The objective of this study is to identify sequence variants in ANGPTL8 gene in Arabs and investigate their association with ANGPTL8 plasma level and clinical parameters.
  
  
  METHODS
  A cross sectional study was designed to examine the level of ANGPTL8 in 283 non-diabetic Arabs, and to identify its sequence variants using Sanger sequencing and their association with various clinical parameters.
  
  
  RESULTS
  Using Sanger sequencing, we sequenced the full ANGPTL8 gene in 283 Arabs identifying two single nucleotide polymorphisms (SNPs) Rs.892066 and Rs.2278426 in the coding region. Our data shows for the first time that Arabs with the heterozygote form of (c.194C > T Rs.2278426) had higher level of Fasting Blood Glucose (FBG) compared to the CC homozygotes. LDL and HDL level in these subjects did not show significant difference between the two subgroups. Circulation level of ANGPTL8 did not vary between the two forms. No significant changes were observed between the various forms of Rs.892066 variant and FBG, LDL or HDL.
  
  
  CONCLUSIONS
  Our data shows for the first time that heterozygote form of ANGPTL8 Rs.2278426 variant was associated with higher FBG level in Arabs highlighting the importance of these variants in controlling the function of betatrophin.
authors: Biochemistry and Molecular Biology Unit, Dasman Diabetes Institute, Kuwait City, Kuwait. mohamed.abufarha@dasmaninstitute.org.
authors: Mohamed
authors: M
authors: Abu-Farha
authors: Dasman Genome Center, Dasman Diabetes Institute, Kuwait City, Kuwait.
authors: Motasem
authors: M
authors: Melhem
authors: Biochemistry and Molecular Biology Unit, Dasman Diabetes Institute, Kuwait City, Kuwait.
authors: Jehad
authors: J
authors: Abubaker
authors: Biochemistry and Molecular Biology Unit, Dasman Diabetes Institute, Kuwait City, Kuwait.|Dasman Genome Center, Dasman Diabetes Institute, Kuwait City, Kuwait.
authors: Kazem
authors: K
authors: Behbehani
authors: Dasman Genome Center, Dasman Diabetes Institute, Kuwait City, Kuwait.
authors: Osama
authors: O
authors: Alsmadi
authors: Sidra Medical and Research Center, Doha, Qatar. nelkum@sidra.org.
authors: Naser
authors: N
authors: Elkum
mesh_terms: D000328:Adult; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D018912:Arabs; D001786:Blood Glucose / Q000378:metabolism; D003430:Cross-Sectional Studies; D003920:Diabetes Mellitus / Q000097:blood* / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007730:Kuwait; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D008875:Middle Aged; D036361:Peptide Hormones / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: C576683:ANGPTL8 protein, human; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D001786:Blood Glucose; D036361:Peptide Hormones