Identification of two common variants contributing to serum apolipoprotein B levels in Mexicans.
OBJECTIVE
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.


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=6.07x10(-6)] and rs1349411 [P=2.72x10(-4)]) that surpassed the significance level for the number of tests performed in the test step (P<3.84x10(-4)). 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.


CONCLUSIONS
We identified two novel variants, rs1349411 and rs1424032, for serum apoB levels in Mexicans.
Weissglas-Volkov
Daphna
D
Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, Calif 90095-7088, USA.
Plaisier
Christopher L
CL
Huertas-Vazquez
Adriana
A
Cruz-Bautista
Ivette
I
Riaño-Barros
Daniela
D
Herrera-Hernandez
Miguel
M
Riba
Laura
L
Cantor
Rita M
RM
Sinsheimer
Janet S
JS
Aguilar-Salinas
Carlos A
CA
Tusie-Luna
Teresa
T
Pajukanta
Päivi
P
D000071479:APOBEC-1 Deaminase; D000328:Adult; D044467:American Indian or Alaska Native / Q000235:genetics*; D001055:Apolipoproteins B / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D003564:Cytidine Deaminase / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D006949:Hyperlipidemias / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008800:Mexico / Q000453:epidemiology; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D012307:Risk Factors
D001055:Apolipoproteins B; D012333:RNA, Messenger; D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; D003564:Cytidine Deaminase