Lipoprotein-genotype associations in Trinidadian neonates.
OBJECTIVE
We hypothesized that common variation in the angiotensinogen (AGT), beta-3-adrenergic receptor, intestinal fatty acid-binding protein, serum paraoxonase, paraoxonase-2, hepatic lipase, apolipoprotein E (APOE), and Werner helicase (WRN) genes would be associated with variation in biochemical phenotypes in a previously unstudied neonatal sample.


METHODS
We examined associations of both nongenetic and genetic variables with plasma lipoprotein traits in neonates from Trinidad.


RESULTS
Among nongenetic variables, we found significant associations between plasma concentrations of: 1) lipoprotein(a) [Lp(a)] and both ethnicity (p = 0.037) and birth weight (p = 0.001); 2) total cholesterol and gender (p = 0.010); 3) triglyceride and birth weight (p = 0.035); and 4) apolipoprotein AI and gender (p = 0.016). Among genetic variables, we found that: 1) common variation on chromosome 1q in AGT codon 235 was significantly associated with variation in plasma apolipoproteins AI (p<0.0001) and B (p = 0.013); 2) common variation in WRN at codon 1367 was significantly associated with variation in plasma Lp(a) (p<0.0001); and 3) common variation in APOE at codons 112 and 158 was significantly associated with variation in plasma triglycerides (p = 0.013).


CONCLUSIONS
The associations with AGT and WRN are novel and may have resulted either from a direct influence of the genetic variants or through linkage disequilibrium with other functional loci, such as the familial combined hyperlipidemia locus on chromosome 1q in the case of AGT. Despite the fact that there are some limitations in making determinations from cord blood, the results suggest that there may be genetic determinants of plasma lipoproteins in neonates.
Hegele
R A
RA
John P. Robarts Research Institute, University of Western Ontario, London, Canada. robert.hegele@rri.on.ca
Ban
M R
MR
Busch
C P
CP
Ramsewak
S
S
Ramdath
D D
DD
D000349:Africa; D000483:Alleles; D000808:Angiotensinogen / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D043303:Aryldialkylphosphatase; D001208:Asia; D044466:Asian People; D044383:Black People; D002352:Carrier Proteins / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics; D004950:Esterases / Q000097:blood / Q000235:genetics; D005090:Exodeoxyribonucleases; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005828:Genetics, Population; D006801:Humans; D007231:Infant, Newborn; D008049:Lipase / Q000235:genetics; D008074:Lipoproteins / Q000097:blood* / Q000235:genetics*; D008297:Male; D018996:Myelin P2 Protein / Q000235:genetics; D009363:Neoplasm Proteins; D010641:Phenotype; D053484:RecQ Helicases; D011943:Receptors, Adrenergic, beta / Q000235:genetics; D022702:Receptors, Adrenergic, beta-3; D014300:Trinidad and Tobago / Q000208:ethnology; D025521:Tumor Suppressor Proteins; D000071657:Werner Syndrome Helicase
D001057:Apolipoproteins E; D002352:Carrier Proteins; C107608:FABP7 protein, human; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D008074:Lipoproteins; D018996:Myelin P2 Protein; D009363:Neoplasm Proteins; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; D025521:Tumor Suppressor Proteins; D000808:Angiotensinogen; D004950:Esterases; D005090:Exodeoxyribonucleases; D008049:Lipase; D043303:Aryldialkylphosphatase; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase