TY - JOUR
T1 - Identification of two common variants contributing to serum apolipoprotein B levels in mexicans
AU - Weissglas-Volkov, Daphna
AU - Plaisier, Christopher L.
AU - Huertas-Vazquez, Adriana
AU - Cruz-Bautista, Ivette
AU - Riaño-Barros, Daniela
AU - Herrera-Hernandez, Miguel
AU - Riba, Laura
AU - Cantor, Rita M.
AU - Sinsheimer, Janet S.
AU - Aguilar-Salinas, Carlos A.
AU - Tusie-Luna, Teresa
AU - Pajukanta, Päivi
PY - 2010/2
Y1 - 2010/2
N2 - BACKGROUND AND PURPOSE-: Although the Mexican population has a high predisposition to dyslipidemias and premature coronary artery disease, this population is underinvestigated for the genetic factors conferring the high susceptibility. This study attempted to determine these genetic factors. METHODS AND RESULTS-: First, we investigated apolipoprotein B (apoB) levels in Mexican extended families with familial combined hyperlipidemia using a two-step testing strategy. In the screening step, we screened 5721 single-nucleotide polymorphisms (SNPs) for linkage signals with apoB. In the test step, we analyzed the 130 SNPs residing in regions of suggestive linkage signals for association with apoB. We identified significant associations with two SNPs (ie, rs1424032 [P=6.07×10] and rs1349411 [P=2.72×10]) that surpassed the significance level for the number of tests performed in the test step (P<3.84×10). Second, these SNPs were tested for replication in Mexican hyperlipidemic case-control samples. The same risk alleles as in the families with familial combined hyperlipidemia were significantly associated (P<0.05) with apoB in the case-control samples. The rs1349411 resides near the apoB messenger RNA editing enzyme (APOBEC1) involved in the processing of APOB messenger RNA in the small intestine. The rs1424032 resides in a highly conserved noncoding region predicted to function as a regulatory element. CONCLUSION-: We identified two novel variants, rs1349411 and rs1424032, for serum apoB levels in Mexicans.
AB - BACKGROUND AND PURPOSE-: Although the Mexican population has a high predisposition to dyslipidemias and premature coronary artery disease, this population is underinvestigated for the genetic factors conferring the high susceptibility. This study attempted to determine these genetic factors. METHODS AND RESULTS-: First, we investigated apolipoprotein B (apoB) levels in Mexican extended families with familial combined hyperlipidemia using a two-step testing strategy. In the screening step, we screened 5721 single-nucleotide polymorphisms (SNPs) for linkage signals with apoB. In the test step, we analyzed the 130 SNPs residing in regions of suggestive linkage signals for association with apoB. We identified significant associations with two SNPs (ie, rs1424032 [P=6.07×10] and rs1349411 [P=2.72×10]) that surpassed the significance level for the number of tests performed in the test step (P<3.84×10). Second, these SNPs were tested for replication in Mexican hyperlipidemic case-control samples. The same risk alleles as in the families with familial combined hyperlipidemia were significantly associated (P<0.05) with apoB in the case-control samples. The rs1349411 resides near the apoB messenger RNA editing enzyme (APOBEC1) involved in the processing of APOB messenger RNA in the small intestine. The rs1424032 resides in a highly conserved noncoding region predicted to function as a regulatory element. CONCLUSION-: We identified two novel variants, rs1349411 and rs1424032, for serum apoB levels in Mexicans.
KW - Apolipoproteins
KW - Association
KW - Cardiovascular disease
KW - Lipids
KW - Mexican population
UR - http://www.scopus.com/inward/record.url?scp=75149145515&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=75149145515&partnerID=8YFLogxK
U2 - 10.1161/ATVBAHA.109.196402
DO - 10.1161/ATVBAHA.109.196402
M3 - Article
C2 - 19965785
AN - SCOPUS:75149145515
SN - 1079-5642
VL - 30
SP - 353
EP - 359
JO - Arteriosclerosis, thrombosis, and vascular biology
JF - Arteriosclerosis, thrombosis, and vascular biology
IS - 2
ER -