Association of an exonic LDHA polymorphism with altered respiratory response in probands at high risk for panic disorder

Robert A Philibert; Jeffrey J Nelson; Harinder K Sandhu; Raymond R Crowe; William H Coryell

doi:10.1002/ajmg.b.10015

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Association of an exonic LDHA polymorphism with altered respiratory response in probands at high risk for panic disorder

Journal article

Peer reviewed

Association of an exonic LDHA polymorphism with altered respiratory response in probands at high risk for panic disorder

Robert A Philibert, Jeffrey J Nelson, Harinder K Sandhu, Raymond R Crowe and William H Coryell

American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.117B(1), pp.11-17

02/2003

DOI: 10.1002/ajmg.b.10015

PMID: 12555229

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Abstract

Panic disorder (PD) is a clinical syndrome characterized by recurrent discrete episodes of fear accompanied by a variety of physiological and psychological symptoms, often with prominent respiratory components. A series of clinical observations has led some investigators to hypothesize that subtle alterations in ventilatory regulation are integral to at least a subtype of PD. In order to identify genetic factors that might predispose individuals to these alterations in ventilatory response, we conducted single stranded conformation polymorphism analysis across the exons of the lactate dehydrogenase A and B genes (LDHA and LDHB) using DNA prepared from 86 subjects previously characterized by respiratory response to a CO(2) challenge with a variable genetic loading for PD. Remarkably, a single conserved LDHA exon 5 haplotype conferred increased risk for a paradoxical ventilatory response pattern to CO(2) inhalation which robustly separated well subjects at high risk for PD from low-risk control subjects. But, comparison of LDHA exon 5 genotypes in PD probands (n = 25) to that of random newborn controls (n = 182) did not demonstrate any significant differences. Given the pivotal role of LDH in the metabolism of lactate, a known inducer of panic attacks, and the dependence of LDH activity on cell pH, we suggest that LDHA polymorphisms may contribute to the variability to CO(2) respiratory challenge.

Genetic Predisposition to Disease

Panic Disorder - etiology

Exons

Isoenzymes - genetics

Pulmonary Ventilation

Gene Frequency

Humans

Risk Factors

Molecular Sequence Data

Carbon Dioxide - administration & dosage

Genotype

Male

L-Lactate Dehydrogenase - drug effects

Polymorphism, Genetic

L-Lactate Dehydrogenase - genetics

Base Sequence

Adolescent

Adult

Female

Isoenzymes - drug effects

Carbon Dioxide - pharmacology

Panic Disorder - genetics

Details

Title: Subtitle: Association of an exonic LDHA polymorphism with altered respiratory response in probands at high risk for panic disorder
Creators: Robert A Philibert - Department of Psychiatry, The University of Iowa, Iowa City, Iowa 52242-1000, USA. robert-philibert@uiowa.edu
Jeffrey J Nelson
Harinder K Sandhu
Raymond R Crowe
William H Coryell
Resource Type: Journal article
Publication Details: American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.117B(1), pp.11-17
DOI: 10.1002/ajmg.b.10015
PMID: 12555229
NLM abbreviation: Am J Med Genet B Neuropsychiatr Genet
ISSN: 1552-4841
eISSN: 1552-485X
Publisher: United States
Grant note: MH 56132 / NIMH NIH HHS
Language: English
Date published: 02/2003
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Psychiatry; Iowa Neuroscience Institute
Record Identifier: 9984003458302771

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