Association of an exonic LDHA polymorphism with altered respiratory response in probands at high risk for panic disorder.
Association of an exonic LDHA polymorphism with altered respiratory response in probands at high risk for panic disorder.
复制标题
外显子 LDHA 多态性与惊恐障碍高风险先证者呼吸反应改变的关联。
DOI：
10.1002/ajmg.b.10015
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Coryell,WilliamH
中科院分区：
文献类型：
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作者：
Philibert,RobertA;Nelson,JeffreyJ;Sandhu,HarinderK;Crowe,RaymondR;Coryell,WilliamH
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 (LDHAandLDHB) using DNA prepared from 86 subjects previously characterized by respiratory response to a CO2challenge with a variable genetic loading for PD. Remarkably, a single conservedLDHAexon 5 haplotype conferred increased risk for a paradoxical ventilatory response pattern to CO2inhalation 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 thatLDHApolymorphisms may contribute to the variability to CO2respiratory challenge. © 2003 Wiley‐Liss, Inc.
