title: Re-sequencing of the APOAI promoter region and the genetic association of the -75G > A polymorphism with increased cholesterol and low density lipoprotein levels among a sample of the Kuwaiti population.
abstract: BACKGROUND
  APOAI, a member of the APOAI/CIII/IV/V gene cluster on chromosome 11q23-24, encodes a major protein component of HDL that has been associated with serum lipid levels. The aim of this study was to determine the genetic association of polymorphisms in the APOAI promoter region with plasma lipid levels in a cohort of healthy Kuwaiti volunteers.
  
  
  METHODS
  A 435 bp region of the APOAI promoter was analyzed by re-sequencing in 549 Kuwaiti samples. DNA was extracted from blood taken from 549 healthy Kuwaiti volunteers who had fasted for the previous 12 h. Univariate and multivariate analysis was used to determine allele association with serum lipid levels.
  
  
  RESULTS
  The target sequence included a partial segment of the promoter region, 5'UTR and exon 1 located between nucleotides -141 to +294 upstream of the APOAI gene on chromosome 11. No novel single nucleotide polymorphisms (SNPs) were observed. The sequences obtained were deposited with the NCBI GenBank with accession number [GenBank: JX438706]. The allelic frequencies for the three SNPs were as follows: APOAI rs670G = 0.807; rs5069C = 0.964; rs1799837G = 0.997 and found to be in HWE. A significant association (p < 0.05) was observed for the APOAI rs670 polymorphism with increased serum LDL-C. Multivariate analysis showed that APOAI rs670 was an independent predictive factor when controlling for age, sex and BMI for both LDL-C (OR: 1.66, p = 0.014) and TC (OR: 1.77, p = 0.006) levels.
  
  
  CONCLUSIONS
  This study is the first to report sequence analysis of the APOAI promoter in an Arab population. The unexpected positive association found between the APOAI rs670 polymorphism and increased levels of LDL-C and TC may be due to linkage disequilibrium with other polymorphisms in candidate and neighboring genes known to be associated with lipid metabolism and transport.
authors.affiliation: Department of Biological Sciences, Faculty of Science, Kuwait University, PO Box 5069, Safat 13060, Kuwait. s.albustan@ku.edu.kw.
authors.forename: Suzanne A
authors.initials: SA
authors.lastname: Al-Bustan
authors.forename: Ahmad E
authors.initials: AE
authors.lastname: Al-Serri
authors.forename: Babitha G
authors.initials: BG
authors.lastname: Annice
authors.forename: Majed A
authors.initials: MA
authors.lastname: Alnaqeeb
authors.forename: Ghada A
authors.initials: GA
authors.lastname: Ebrahim
mesh_terms: D020121:5' Untranslated Regions; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000483:Alleles; D016632:Apolipoprotein A-I / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood*; D002880:Chromosomes, Human, Pair 11; D015331:Cohort Studies; D005091:Exons; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007730:Kuwait; D015810:Linkage Disequilibrium; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D012737:Sex Factors; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
chemical_list: D020121:5' Untranslated Regions; D016632:Apolipoprotein A-I; D008077:Lipoproteins, LDL; D014280:Triglycerides; D002784:Cholesterol
references.citation: Genet Epidemiol. 1994;11(3):265-80
references.pmid: 8088507
references.citation: Nucleic Acids Res. 1988 Feb 11;16(3):1215
references.pmid: 3344216
references.citation: Behav Res Methods. 2007 May;39(2):175-91
references.pmid: 17695343
references.citation: Exp Gerontol. 2009 Mar;44(3):136-60
references.pmid: 19041386
references.citation: Genet Epidemiol. 1996;13(1):1-10
references.pmid: 8647374
references.citation: Arterioscler Thromb Vasc Biol. 1995 Oct;15(10):1740-5
references.pmid: 7583551
references.citation: Clin Genet. 2006 Mar;69(3):263-70
references.pmid: 16542392
references.citation: Nat Genet. 2013 Jan;45(1):25-33
references.pmid: 23202125
references.citation: Angiology. 2010 Feb-Mar;61(1):42-8
references.pmid: 19398424
references.citation: Int J Mol Med. 2008 Jun;21(6):753-64
references.pmid: 18506369
references.citation: J Mol Med (Berl). 2006 Jul;84(7):561-72
references.pmid: 16705465
references.citation: Pediatr Res. 2001 Apr;49(4):514-8
references.pmid: 11264435
references.citation: Arterioscler Thromb Vasc Biol. 1996 Dec;16(12):1416-23
references.pmid: 8977444
references.citation: Atherosclerosis. 1996 Dec 20;127(2):255-62
references.pmid: 9125316
references.citation: Endocrine. 2012 Feb;41(1):103-10
references.pmid: 22105741
references.citation: J Clin Endocrinol Metab. 2010 Dec;95(12):E500-10
references.pmid: 20826588
references.citation: J Biol Chem. 1994 Jul 1;269(26):17371-4
references.pmid: 8021234
references.citation: J Clin Endocrinol Metab. 2012 Feb;97(2):E248-56
references.pmid: 22090275
references.citation: N Engl J Med. 1993 Apr 22;328(16):1150-6
references.pmid: 8455681
references.citation: Clin Genet. 1991 Jan;39(1):1-5
references.pmid: 1900041
references.citation: Circ Res. 2004 Apr 16;94(7):993-9
references.pmid: 15001527
references.citation: Trends Biochem Sci. 2007 Feb;32(2):71-7
references.pmid: 17215125
references.citation: Control Clin Trials. 1990 Apr;11(2):116-28
references.pmid: 2161310
references.citation: Proc Nutr Soc. 2001 Aug;60(3):329-39
references.pmid: 11681807
references.citation: Arterioscler Thromb Vasc Biol. 1999 Feb;19(2):348-55
references.pmid: 9974418
references.citation: Genet Epidemiol. 1999;16(2):205-22
references.pmid: 10030402
references.citation: J Lipid Res. 2010 Jul;51(7):1823-31
references.pmid: 20308432
references.citation: Annu Rev Genet. 2000;34:233-254
references.pmid: 11092828
references.citation: Hum Biol. 2004 Apr;76(2):307-12
references.pmid: 15359539
references.citation: J Lipid Res. 1995 Feb;36(2):211-28
references.pmid: 7751809
references.citation: In Vivo. 2011 May-Jun;25(3):425-30
references.pmid: 21576418
references.citation: J Clin Invest. 1992 Jun;89(6):1796-800
references.pmid: 1601989
references.citation: Nature. 2010 Aug 5;466(7307):707-13
references.pmid: 20686565
references.citation: Int J Cardiol. 2005 Jul 10;102(2):309-14
references.pmid: 15982502
references.citation: Twin Res Hum Genet. 2007 Oct;10(5):703-11
references.pmid: 17903110
references.citation: Eur J Epidemiol. 2009;24(12):763-74
references.pmid: 19888660
references.citation: Braz J Med Biol Res. 2005 Apr;38(4):535-41
references.pmid: 15962178
references.citation: Hum Hered. 2006;61(2):87-96
references.pmid: 16710093
references.citation: Circulation. 1996 Oct 1;94(7):1622-8
references.pmid: 8840853
references.citation: Nat Genet. 2009 Jan;41(1):47-55
references.pmid: 19060911
references.citation: Ann Saudi Med. 2003 May-Jul;23(3-4):162-6
references.pmid: 16985307
references.citation: J Hum Genet. 2004;49(8):433-439
references.pmid: 15258834
references.citation: Hum Biol. 2005 Aug;77(4):487-98
references.pmid: 16485778
references.citation: J Lipid Res. 1990 Aug;31(8):1371-7
references.pmid: 1980685
references.citation: Circ Cardiovasc Genet. 2008 Oct;1(1):21-30
references.pmid: 19802338
references.citation: Lipids Health Dis. 2011 Aug 19;10:140
references.pmid: 21854571
references.citation: Atherosclerosis. 2006 Jan;184(1):113-20
references.pmid: 16326171
references.citation: Indian J Hum Genet. 2011 Sep;17(3):194-200
references.pmid: 22345992
references.citation: Biochim Biophys Acta. 1998 May 29;1398(1):67-74
references.pmid: 9602064
references.citation: FEBS Lett. 1992 Jun 8;304(1):98-101
references.pmid: 1618307
references.citation: Clin Genet. 2002 Mar;61(3):176-84
references.pmid: 12000358