Family-based transmission disequilibrium test (TDT) and case-control association studies reveal surfactant protein A (SP-A) susceptibility alleles for respiratory distress syndrome (RDS) and possible race differences
Family-based transmission disequilibrium test (TDT) and case-control association studies reveal surfactant protein A (SP-A) susceptibility alleles for respiratory distress syndrome (RDS) and possible race differences
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DOI：
10.1034/j.1399-0004.2001.600303.x
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发表时间：
2001-09-01
影响因子：
3.5
通讯作者：
Merrill, J
中科院分区：
文献类型：
--
作者：
Floros, J;Fan, R;Merrill, J
早产儿呼吸窘迫综合征（RDS）的一个关键原因是缺乏肺表面活性物质（一种脂蛋白复合物）。低水平的表面活性剂蛋白 A (SP-A) 和 SP-A 等位基因均与 RDS 相关。使用候选基因方法，我们进行了基于家族的连锁研究，以辨别 SP-A 与 RDS 的连锁并确定 SP-A 易感性或保护性等位基因。此外，我们对白人和黑人进行了病例对照研究，以检测 RDS 和 SP-A 等位基因之间的关联。传递不平衡检验（TDT）分析显示，RDS中等位基因6A（2）和1A（0）以及1A（0）/6A（2）单倍型的传递频率（从父母到RDS后代）增加，而等位基因1A（5）和6A（4）以及单倍型1A（5）/6A（4）的传递频率减少。扩展 TDT 分析进一步强化了观察结果。病例对照研究表明，在患有RIDS的白人或黑人中，特定基因型1A(0)和6A(2)或1A(0)的频率分别增加，但特定6A(3)基因型的频率在某些白人亚组中增加，而在黑人中减少。回归分析显示胎龄 (GA) 和 6A(3) 基因型是黑人 RDS 的重要因素。对于患有 RDS 的白人，GA 和产前类固醇是重要因素。这些数据共同表明 SP-A 和 RDS 之间的联系；某些 SP-A 等位基因/单倍型是 RDS 的易感性（1A(0)、6A(2)、1A(0)/6A(2)）或保护性（1A(5)、6A(4)、1A(5)/6A(4)）因素。黑人和白人之间在 SP-A 等位基因方面可能存在一些差异。
A key cause of respiratory distress syndrome (RDS) in the prematurely born infant is deficiency of pulmonary surfactant, a lipoprotein complex. Both low levels of surfactant protein A (SP-A) and SP-A alleles have been associated with RDS. Using the candidate gene approach, we performed family-based linkage studies to discern linkage of SP-A to RDS and identify SP-A susceptibility or protective alleles. Moreover, we performed case-control studies of whites and blacks to detect association between RDS and SP-A alleles. Transmission disequilibrium test (TDT) analysis revealed that the frequency of transmission (from parent to the offspring with RDS) of alleles 6A(2) and 1A(0) and of 1A(0)/6A(2) haplotype in RDS was increased, whereas transmission of alleles 1A(5) and 6A(4) and of haplotype 1A(5)/6A(4) was decreased. Extended TDT analysis further strengthened the observations made. The case-control studies showed that in whites or blacks with RIDS the frequencies of specific genotypes, 1A(0) and 6A(2) or 1A(0) were increased respectively,,, but the frequency of specific 6A(3) genotypes was increased in certain white subgroups and decreased in blacks. Regression analysis revealed gestational age (GA) and 6A(3) genotypes are significant factors in blacks with RDS. In whites with RDS, GA and antenatal steroids are important factors. The data together indicate linkage between SP-A and RDS; certain SP-A alleles/haplotypes are susceptibility (1A(0), 6A(2), 1A(0)/6A(2)) or protective (1A(5), 6A(4), 1A(5)/6A(4)) factors for RDS. Some differences between blacks and whites with regard to SP-A alleles may exist.