A common variant association study in ethnic Saudi Arabs reveals novel susceptibility loci for hypertriglyceridemia.
Hypertriglyceridemia (hTG) is a lipid disorder, resulting from an elevation in triglyceride levels, with a strong genetic component. It constitutes a significant risk factor for coronary artery disease (CAD), a leading cause of death worldwide. In this study, we performed a common variant association study for hTG in ethnic Saudi Arabs. We genotyped 5501 individuals in a two-phase experiment using Affymetrix Axiom®Genome-Wide CEU 1 Array (Affymetrix, Santa Cruz, CA) that contains a total of 587,352 single nucleotide polymorphisms (SNPs). The lead variant was the rs1558861 [1.99 (1.73-2.30); p = 7.37 × 10-22], residing on chromosome (chr) 11 at the apolipoprotein A-I/A-5 (APOA1/APOA5) locus. The rs780094 [1.34 (1.21-1.49); p = 8.57 × 10-8] on chr 2 at the glucokinase regulatory protein (GCKR) locus was similarly significantly associated, while the rs10911205 [1.29 (1.16-1.44); p = 3.52 × 10-6] on chr1 at the laminin subunit gamma-1 (LAMC1) locus showed suggestive association with disease. Furthermore, the rs17145738 [0.68 (0.60-0.77); p = 6.69 × 10-9] on chr7 at the carbohydrate-responsive element-binding protein-encoding (MLXIPL) gene locus displayed significant protective characteristics, while another variant rs6982502 [0.76 (0.68-0.84); p = 5.31 × 10-7] on chr8 showed similar but weaker properties. These findings were replicated in 317 cases vs 1415 controls from the same ethnic Arab population. Our study identified several variants across the human genome that are associated with hTG in ethnic Arabs.
Centre for Diabetes Research, The Harry Perkinsn Institute for Medical Research, Perth, WA, Australia.|Centre for Medical Research, University of Western Australia, Perth, WA, Australia.
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R
Ram
Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, KSA.
S M
SM
Wakil
Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, KSA.
N P
NP
Muiya
Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, KSA.
E
E
Andres
Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, KSA.
N
N
Mazhar
Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, KSA.
S
S
Hagos
King Faisal Heart Institute, King Faisal Specialist Hospital and Research Centre, Riyadh, KSA.
M
M
Alshahid
Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, KSA.
B F
BF
Meyer
Centre for Diabetes Research, The Harry Perkinsn Institute for Medical Research, Perth, WA, Australia.|Centre for Medical Research, University of Western Australia, Perth, WA, Australia.
G
G
Morahan
Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, KSA.
N
N
Dzimiri
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D016632:Apolipoprotein A-I / Q000235:genetics*; D000072040:Apolipoprotein A-V / Q000235:genetics*; D018912:Arabs / Q000235:genetics; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics*; D003324:Coronary Artery Disease / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015228:Hypertriglyceridemia / Q000235:genetics* / Q000503:physiopathology; D007797:Laminin / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012529:Saudi Arabia
C505693:APOA1 protein, human; C437704:APOA5 protein, human; D048868:Adaptor Proteins, Signal Transducing; D016632:Apolipoprotein A-I; D000072040:Apolipoprotein A-V; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C485100:GCKR protein, human; D007797:Laminin; C116385:MLXIPL protein, human; C089141:laminin gamma 1
APOA1/APOA5 gene cluster; GCKR; LAMC1; MLXIPL; TRIB1; common variants association study; meta-analysis