慢性阻塞性肺病患者低氧呼吸驱动降低的遗传学初步研究

A genetic study of the depressive respiratory responses to hypoxia in chronic obstructive pulmonary disease patients with type Ⅱ respiratory failure *

目的 观测慢性阻塞性肺病 (chronic obstructive pulmonary disease,COPD) 型呼吸衰竭患者及其子女呼吸中枢对低氧的反应性 ,并对低氧呼吸驱动与微卫星位点的关系进行连锁分析 ,初步探讨其低氧呼吸驱动反应性降低的基因是否与染色体 6 q2 1.1- 2 1.2区域的某一位点相连锁。方法 测定 6例COPD 型呼吸衰竭患者及其 2 1名子女呼吸中枢驱动对低氧的反应性 ΔP0 .1 / ΔSa O2 、ΔVE/ ΔSa O2 ,同时对位于第 6号染色体短臂上的 5个微卫星位点 D6 S2 99、D6 S16 91、D6 S2 76、D6 S170 1、D6 S16 2 9进行扩增片段长度多态性检验 ,用 L INKAGE遗传统计软件进行连锁分析。结果 受检患者的 10名子女低氧呼吸驱动反应性降低 ,而另 11名子女则正常 ,两组子女的性别分布均等 ;低氧呼吸驱动反应性降低性状与各微卫星位点的连锁分析结果显示 ,最大 L od值在 D6 S2 76位点为 1.74(θ=0 .10 )。结论 低氧呼吸驱动反应性降低可能受遗传因素的影响 ,且遗传方式符合常染色体显性遗传 ;致低氧呼吸驱动反应性降低的基因与D6 S2

Objective The depression of the ventilatory and P 0.1 responses to hypoxia and hypercapnia may play an important role in the development of CO 2 retention in the patients with chronic obstructive pulmonary disease (COPD). The purpose of this study was to investigate if there is any linkage relationship between the depressed ventilatory and P 0.1 response phenotypes and the microsatellite markers on chromosome 6q21.1 21.2 among Chinese people.Methods P 0.1 and ventilatory responses to hypoxia were measured in six COPD patients with type Ⅱ respiratory failure, as well as in their 21 normal adult offsprings. Polymerase chain reaction (PCR), denaturing polyacrylamide gel electrophoresis and silver staining techniques were used to study the amplified fragment length polymorphism. Linkage analysis was done with the LINKAGE program.Results Hypoxia response was low in 10 offsprings, and normal in the other 11 offsprings. Linkage analysis showed the maximum Lod score was 1.74(D6S276,θ=0.10).Conclusion The depressed hypoxia response might have been influenced by genetic factors. The model was in accord with autosomal dominant inheritance. The disease related gene was linked to D6S276 locus.