Association of ApoE genetic variants with obstructive sleep apnea in children.
OBJECTIVE
Although several studies have reported an association between obstructive sleep apnea (OSA) and the chromosomal region containing the Apolipoprotein E (ApoE) gene, findings about the exact location in the ApoE gene have been inconsistent. The objective of our study was thus to determine the allele, genotype, and haplotype frequencies at several single nucleotide polymorphisms (SNPs) in the region of ApoE and test their association with OSA status in children.


METHODS
Caucasian children, ranging in age from 2 to 21 years, with polysomnographic evidence of OSA (>1 obstructive apnea or obstructive hypopnea episodes per hour of sleep) were recruited in the case group. Our race- and gender-matched control group was recruited from a population-based cohort of children enrolled in the Princeton School District Study.


RESULTS
Comparison of allele and genotype frequencies between cases (n=92) and controls (n=92) revealed significant differences for SNPs rs405509 and rs7412. Multivariate logistic regression analysis with age and body mass index (BMI) as covariates revealed a significant association between OSA status and SNPs rs157580, rs405509, rs769455 and rs7412. The sliding window haplotype trend regression test revealed that SNP rs405509 was included in all haplotypes that are significantly associated with OSA status.


CONCLUSIONS
We conclude that polymorphisms involving more than one locus in the ApoE gene and its regulatory region are associated with OSA in children. Further studies replicating these findings in different populations are needed as are studies involving fine mapping of this region.
Kalra
Maninder
M
Division of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, United States. maninder.kalra@cchmc.org
Pal
Prodipto
P
Kaushal
Ritesh
R
Amin
Raouf S
RS
Dolan
Lawrence M
LM
Fitz
Kelly
K
Kumar
Sunil
S
Sheng
Xiaohua
X
Guha
Saurav
S
Mallik
Joydeep
J
Deka
Ranjan
R
Chakraborty
Ranajit
R
D000293:Adolescent; D000328:Adult; D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017286:Polysomnography; D012307:Risk Factors; D020181:Sleep Apnea, Obstructive / Q000235:genetics*
D001057:Apolipoproteins E