Can Mu-opioid Receptor A118G Gene Polymorphism be Predictive of Acute Poisoning Severity in the Emergency Department?

To the Editor,We have read with a great interest the manuscript by Maninietal.[1]reportingtheassociationofmu-opioidreceptorgene(OPRM1) A118G polymorphism with clinical severity ofacute poisonings admitted to the emergency department. Inpatients carrying at least one G allele of the c.A118G poly-morphism (rs1799971), these authors reported increasedpoisoning severity defined as the occurrence of respiratoryarrest, cardiac arrest, or in-hospital mortality with an adjust-ed 5.3 odds ratio whatever the responsible drug was.This finding is quite promising since suggesting that onesimple test could be helpful in identifying acutely poisonedpatients with major risk for severe outcome. However, sev-eral significant biases may temperate possible enthusiasm.The association between the 118G allele and poisoningseverity may have resulted from a confounding factor, i.e.,the surprising severity of poisonings with opioids and benzo-diazepines reported in Manini’s patient population as assessedin the univariate analysis (Table 2) and confirmed in themultivariate analysis identifying a significant link betweenthe clinical outcome and recreational intent of drug abuse(Table4).Toouropinion,theauthorsshouldhavelimitedtheiranalysisto the group oftoxicants witheither obvious(opioids)or possible molecular interactions with MOR like previouslyreported(benzodiazepines)[2],whileothertoxicantslikesym-pathomimetics, antipsychotics, and antidepressants do notclearly interact with MOR.Previous studies have associated the 118G allele with lessmorphine-related pupil-constricting and gastrointestinaleffects [3] and no increased respiratory depression [4]. Amore recent study has evidenced that infants with neonatalabstinence syndrome due to in utero exposure to opioidsneeded less treatments and presented shortened length ofstay, if carrying almost one 118G allele [5]. Taken together,all these data support increased resistance rather than in-creased susceptibility or vulnerability to opioids in the pres-ence of the 118G allele, in contrast to Manini’s findings [1].Additionally, as partly acknowledged by the authors, wecannot exclude that ethnical differences according to severityexplain the observed association between the 118G allele andsevere poisoning outcome, sin cethe118Galleleismorecom-moninAsiandescent( http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=1799971).Thus,webelievethatdeterminationofpatients’ ethnical origin is mandatory to allow any definitiveconclusion, even though the Hardy –Weinberg Equilibrium isrespected. Moreover, we cannot e xclude that ethnical origin isassociated with socioeconomical factors or morbidities thatmayhavecontributedtoworsenthefinaloutcomeofpoisoning.Inconclusion,Manini’sdataarequitepromisingtoperson-alizemonitoringofpoisonedpatients,especiallythatthe118Gallele is frequent in the general population. However, consid-ering possible major limitations of their study, a reproductionin a well-characterized independent cohort appears necessary.References