Faculty Collaboration Database

Perioperative genomic profiles using structure-specific oligonucleotide probes. Clin Med Res 2009 Sep;7(3):69-84

Date

05/29/2009

Pubmed ID

19474452

Pubmed Central ID

PMC2757430

DOI

10.3121/cmr.2009.837

Scopus ID

2-s2.0-70449340661 (requires institutional sign-in at Scopus site)   10 Citations

Abstract

OBJECTIVES: Many complications in the perioperative interval are associated with genetic susceptibilities that may be unknown in advance of surgery and anesthesia, including drug toxicity and inefficacy, thrombosis, prolonged neuromuscular blockade, organ failure and sepsis. The aims of this study were to design and validate the first genetic testing platform and panel designed for use in perioperative care, to establish allele frequencies in a target population, and to determine the number of mutant alleles per patient undergoing surgery. DESIGN/SETTING/PARTICIPANTS AND METHODS: One hundred fifty patients at Marshfield Clinic, Marshfield, Wisconsin, 100 patients at the Medical College of Wisconsin Zablocki Veteran's Administration Medical Center, Milwaukee, Wisconsin, and 200 patients at the University of Wisconsin Hospitals and Clinics, Madison, Wisconsin undergoing surgery and anesthesia were tested for 48 polymorphisms in 22 genes including ABC, BChE, ACE, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, beta2AR, TPMT, F2, F5, F7, MTHFR, TNFalpha, TNFbeta, CCR5, ApoE, HBB, MYH7, ABO and Gender (PRKY, PFKFB1). Using structure-specific cleavage of oligonucleotide probes (Invader, Third Wave Technologies, Inc., Madison, WI), 96-well plates were configured so that each well contained reagents for detection of both the wild type and mutant alleles at each locus.

RESULTS: There were 21,600 genotypes confirmed in duplicate. After withdrawal of polymorphisms in non-pathogenic genes (i.e., the ABO blood group and gender-specific alleles), 376 of 450 patients were found to be homozygous for mutant alleles at one or more loci. Modes of two mutant homozygous loci and 10 mutant alleles in aggregate (i.e., the sum of homozygous and heterozygous mutant polymorphisms) were observed per patient.

CONCLUSIONS: Significant genetic heterogeneity that may not be accounted for by taking a family medical history, or by obtaining routine laboratory test results, is present in most patients presenting for surgery and may be detected using a newly developed genotyping platform.

Author List

Hogan KJ, Burmester JK, Caldwell MD, Hogan QH, Coursin DB, Green DN, Selzer RM, Broderick TP, Rusy DA, Poroli M, Lutz AL, Sanders AM, Oldenburg MC, Koelbl JA, de Arruda-Indig M, Halsey JL, Day SP, Domanico MJ

Author

Quinn H. Hogan MD Professor in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Alleles
Anesthesia
Female
Genetic Predisposition to Disease
Genetic Variation
Genomics
Genotype
Homozygote
Humans
Male
Models, Biological
Molecular Diagnostic Techniques
Oligonucleotides
Pharmacogenetics
Polymerase Chain Reaction
Preoperative Period