Sudden infant death syndrome (SIDS) and polymorphisms in Monoamine Oxidase A gene (MAOA): a revisit

Abstract

Literature describes multiple possible links between genetic variations in the neuroadrenergic system and the occurrence of sudden infant death syndrome. The X-chromosomal Monoamine oxidase A (MAOA) is one of the genes with regulatory activity in the noradrenergic and serotonergic neuronal systems and a polymorphism of the promoter which affects the activity of this gene has been proclaimed to contribute significantly to the prevalence of sudden infant death syndrome (SIDS) in three studies from 2009, 2012 and 2013. However, these studies described different significant correlations regarding gender or age of children. Since several studies, suggesting associations between genetic variations and SIDS, were disproved by follow-up analysis, this study was conducted to take a closer look at the MAOA gene and its polymorphisms. The functional MAOA promoter length polymorphism was investigated in 261 SIDS cases and 93 control subjects. Moreover, the allele distribution of 12 coding and non-coding single nucleotide polymorphisms (SNPs) of the MAOA gene was examined in 285 SIDS cases and 93 controls by a minisequencing technique. In contrast to prior studies with fewer individuals, no significant correlations between the occurrence of SIDS and the frequency of allele variants of the promoter polymorphism could be demonstrated, even including the results from the abovementioned previous studies. Regarding the SNPs, three statistically significant associations were observed which had not been described before. This study clearly disproves interactions between MAOA promoter polymorphisms and SIDS, even if variations in single nucleotide polymorphisms of MAOA should be subjected to further analysis to clarify their impact on SIDS.

Association between monoamine oxidase A promoter polymorphism and the risk of sudden infant death syndrome: a meta-analysis

“…Thus, the total number of X-chromosomes analyzed in all the included studies was 1423 and 1566 in the case group and the control group, respectively. To clarify, Gross et al [ 28 ] presented a pooled control group including the uSID and healthy individuals examined in their study, as well as the data from the study of Courts et al [ 22 ] and Klintschar et al [ 23 ]. To avoid potential bias, the number of control group examined in the study of Gross et al was calculated by excluding those in the other two studies (Courts et al: 280 controls, including 109 females and 171 males; Klintschar et al: 260 controls, including 99 females and 151 males) from the pooled controls (585 controls, including 227 females and 358 males).…”

“…The number of subjects with different alleles and genotypes is shown in Table 2 . It is worth mentioning that in the study of Gross et al [ 28 ], the number of enrolled infants did not match the data presented in their table “Allele distribution of MAOA promoter polymorphism in this study’s SIDS cases and controls” (Number of X chromosomes analyzed: all SIDS, SIDS n = 368, control n = 812; male, SIDS n = 154, control n = 358; female, SIDS n = 214, control n = 454). Accordingly, they have successfully examined a total of 261 SIDS cases including 154 male cases and 107 female cases.…”

“…The effect of each individual study on the total results was estimated by removing the results of the studies one by one to observe the change that occurs in the overall results. After excluding the study of Gross et al [ 28 ], the study with the largest population among the included studies, a statistically significant protective influence of 3R/3R polymorphism emerged among females (OR = 0.61, 95% CI = 0.37–0.98, P = 0.04). The stability of other comparisons conducted on male infants was not affected by removing any of the studies.…”

“…A total of six independent case-control studies [21][22][23][26][27][28], including 1022 SIDS victims and 1150 controls, were selected in this meta-analysis. Among the included subjects, 401 females were classified into the case group and 416 females were classified into the control group.…”

Systems-level perspective of sudden infant death syndrome

“…Chief among these are the neuronal signaling components MAOA, PHOX2B and SLC6A4, where multiple studies have evaluated specific variants in SIDS (54–62). Only in the case of MAOA, are there independent studies, which demonstrate the significant enrichment of a genetic variant in SIDS cases (promoter length polymorphisms) relative to controls (54, 55), however, there are an equal number of studies that dispute this claim (56, 57). MAOA is an attractive candidate molecular regulator, as it is encoded on the X-chromosome and hence may influence the greater propensity of male infants to succumb to SIDS.…”