Whole Genome Sequence Analysis of Candidate Genes Identified Three Loci Potentially Related to Mefloquine Side Effects

Whole Genome Sequence Analysis of Candidate Genes Identified Three Loci Potentially Related to Mefloquine Side Effects Monique Hollis-Perry1, Joshua Gray1, Dutchabong Shaw1,2, Daniel Hupalo1,2, Heidi Adams1,2, Xijun Zhang1,2, Matthew D. Wilkerson1, Lydia D. Hellwig1,2, Clifton Dalgard1, Jeffrey Livezey1, David Saunders1 1Uniformed Services University of Health Sciences Bethesda, MD; 2Henry Jackson Foundation for the Advancement of Military Medicine Bethesda, MD Gene Provided Data RSID Chr loc hg38 Site 1 ref/alt Site 2 ref/alt Site details ORM1 S rs17650,rs1126801 chr9 114323246. ; 114325132 G,G G,G ARG(CGG)20,VAL(GTG)156 ORM1 F1 rs17650,rs1126801 chr9 114323246. ; 114325132 G,A G,G GLN(CAG)20,VAL(GTG)156 ORM1 F2 rs17650,rs1126801 chr9 114323246. ; 114325132 G,A G,A GLN(CAG)20 MET(ATG)156 MTHFR A1298C rs1801131 chr1 11794419 A C p.Glu429Ala MTHFR C677T rs1801133 chr1 11796321 C T p.Ala222Val MDR1 C1236T rs1128503 chr7 87550285 A G p.Gly412Gly MDR1 G2677T rs2032582 chr7 87531302 A C p.Ala893Ser MDR1 C3435T rs1045642 chr7 87509329 A G p.Ile1145Ile PYK2 rs2883490 rs28834970 chr8 27337604 T C intronic HT2A rs7997012 rs7997012 chr13 46837850 A G intronic HT2A rs1928040 rs1928040 chr13 46873101 G A intronic HT2A rs6311 rs6311 chr13 46897343 C T intronic HT2A rs6313 rs6313 chr13 46895805 G A p.Ser34Ser ADA G22A rs73598374 chr20 44651586 C T p.Asp8Tyr ADORA2A (A2A) T1976C rs5751876 chr22 24441333 T C p.Tyr361Tyr ADORA2A (A2A) C2592T rs35320474 chr22 24441942 - T 3' UTR variant METHODS Volunteers with a history of exposure to mefloquine with or without adverse neuropsychiatric symptoms were invited to participate in this case-control cross-sectional study after interviews and medical records review. Investigators searched for potential associations within 7 candidate genes and 16 associated variants for study. Blood samples were collected in Paxgene RNA tubes from 50 volunteers. Mefloquine exposure was defined as: travel to an area with malaria prophylaxis recommendations; w
RITM0040216
Although mefloquine provides effective once-weekly antimalarial prophylaxis, this medication has fallen out of favor due to the risk of neuropsychiatric effects. These can appear after one or two doses, may be mild or severe and commonly include headaches, memory impairment, anxiety or depression, hallucinations, insomnia, and psychosis. Adverse events typically resolve after drug discontinuation, but some patients report long-term complications. While genetic susceptibilities have been identified, pharmacogenomic testing guidance for mefloquine use is not currently available.