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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 (<jats:italic>LDHA<\/jats:italic> and <jats:italic>LDHB<\/jats:italic>) using DNA prepared from 86 subjects previously characterized by respiratory response to a CO<jats:sub>2<\/jats:sub> challenge with a variable genetic loading for PD. Remarkably, a single conserved <jats:italic>LDHA<\/jats:italic> exon 5 haplotype conferred increased risk for a paradoxical ventilatory response pattern to CO<jats:sub>2<\/jats:sub> inhalation which robustly separated well subjects at high risk for PD from low\u2010risk control subjects. But, comparison of LDHA exon 5 genotypes in PD probands (n\u2009=\u200925) to that of random newborn controls (n\u2009=\u2009182) 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 <jats:italic>LDHA<\/jats:italic> polymorphisms may contribute to the variability to CO<jats:sub>2<\/jats:sub> respiratory challenge. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.b.10015","type":"journal-article","created":{"date-parts":[[2003,1,29]],"date-time":"2003-01-29T15:36:34Z","timestamp":1043854594000},"page":"11-17","source":"Crossref","is-referenced-by-count":14,"title":["Association of an exonic <i>LDHA<\/i> polymorphism with altered respiratory response in probands at high risk for panic disorder"],"prefix":"10.1002","volume":"117B","author":[{"given":"Robert A.","family":"Philibert","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey 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