Genetic Association Study of Acetylcholinesterase (ACHE) and Butyrylcholinesterase (BCHE) Variants in Sudden Infant Death Syndrome (SIDS)

Abstract

Background: Sudden infant death syndrome (SIDS) is the leading cause of death among infants aged between one month and one year. Altered enzyme activities or expression of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) have been observed in SIDS patients that might lead to disturbed autonomic function and, together with other risk factors, might trigger SIDS. To explore the contribution of AChE and BChE from a genomic viewpoint, we sought to investigate the association between SIDS and selected single nucleotide polymorphisms (SNPs) in the ACHE and BCHE genes.

Methods: In this case-control study, 13 potentially regulatory SNPs were selected from ACHE and BCHE and were genotyped in 201 SIDS cases and 338 controls. The association of SIDS with the 11 successfully genotyped candidate variants was examined using statistical analyses of overall or stratified cases and haplotype analyses.

Results: No significant overall associations were observed between SIDS and ACHE and BCHE variants in allele, genotype, and haplotype analyses. In subgroup analyses, eight variants were found to be nominally associated with SIDS, though these associations did not remain statistically significant after correction for multiple comparisons. One haplotype (T-C-G-C-C in rs3495-rs1803274-rs1355538-rs2048493-rs1126680) of BCHE was associated with the female SIDS subgroup (57.3% in controls vs. 46.3% in female SIDS cases, p = 0.010).

Conclusions: The selected variants in ACHE and BCHE were not overall associated with SIDS in this study, and thus cannot generally explain the previously reported dysregulation of enzyme activities in SIDS. However, some evidence of association in subgroups and a possible contribution of variants other than those tested here would need to be explored in larger studies.

Keywords: ACHE; BCHE; genetic association; polymorphisms; sudden infant death syndrome (SIDS).

Figure 1

Genomic structure of human ACHE and BCHE, highlighting the locations of selected SNPs. Exons are represented by boxes, untranslated regions are depicted in white, and translated regions are delineated in black.

Figure 2

Linkage disequilibrium (LD) patterns in the ACHE and BCHE genes in a cohort of 539 subjects. Black squares denote regions of strong LD. The values within the cells indicate pairwise degrees of LD, expressed as D’ × 100.