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新生儿暂时性呼吸急促(TTN):β-肾上腺素能受体(ADRB)编码基因多态性的作用?

Transient tachypnea of the newborn (TTN): a role for polymorphisms in the beta-adrenergic receptor (ADRB) encoding genes?

作者信息

Aslan Ece, Tutdibi Erol, Martens Swantje, Han Yihua, Monz Dominik, Gortner Ludwig

机构信息

Center of Pediatrics and Neonatology, Children's University Hospital of Saarland, Homburg/Saar, Germany.

出版信息

Acta Paediatr. 2008 Oct;97(10):1346-50. doi: 10.1111/j.1651-2227.2008.00888.x. Epub 2008 Jun 5.

Abstract

AIM

Transient tachypnea of the newborn (TTN) is a common cause of early respiratory distress in the neonatal period of term infants. Delayed resorption of foetal lung fluid after birth is considered as the main pathophysiological factor. As resorption of foetal lung fluid is a catecholamine dependent process, we aimed at investigating, whether beta1- and beta2-adrenoreceptor (ADRB1, ADRB2) polymorphisms, known to alter catecholamine activity, are operative in TTN.

METHODS

DNA was collected for genotyping from 73 term newborns suffering from TTN and 55 healthy controls from a Caucasian cohort.

RESULTS

TTN infants were more likely to be male (70% vs. 49%; p < 0.05), had a lower mean birthweight (3120 +/- 450 vs. 3396 +/- 504 g; p < 0.001) and gestational age (GA) (38.4 +/- 1.2 vs. 39.4 +/- 1.3 weeks; p < 0.001) and were more often delivered by caesarean section (CS) (71% vs. 26%; p < 0.001). The beta1Ser49Gly polymorphism differed significantly between cases and controls. Multivariate analysis provided beta1Gly49 homozygotes with higher risk for TTN (OR 18.5; 95%CI 1.5-229; p = 0.023) than beta1Ser49 allele carrier. Further analysis showed significant association of T-47C, A46G, C79G and C491T (TACC) haplotype in ADRB2 gene with TTN (p = 0.048).

CONCLUSION

We conclude that beta1Gly49 homozygosity and TACC haplotype of ADRB2 gene, both loss-of-function genetic variations, may predispose to TTN.

摘要

目的

新生儿暂时性呼吸急促(TTN)是足月儿新生儿期早期呼吸窘迫的常见原因。出生后胎儿肺液吸收延迟被认为是主要的病理生理因素。由于胎儿肺液的吸收是一个依赖儿茶酚胺的过程,我们旨在研究已知会改变儿茶酚胺活性的β1和β2肾上腺素能受体(ADRB1、ADRB2)多态性是否在TTN中起作用。

方法

从一个白种人队列中收集了73例患TTN的足月儿新生儿和55例健康对照的DNA进行基因分型。

结果

TTN患儿男性比例更高(70%对49%;p<0.05),平均出生体重更低(3120±450对3396±504g;p<0.001),胎龄(GA)更低(38.4±1.2对39.4±1.3周;p<0.001),剖宫产(CS)分娩的比例更高(71%对26%;p<0.001)。病例组和对照组之间β1Ser49Gly多态性存在显著差异。多变量分析显示β1Gly49纯合子患TTN的风险高于β1Ser49等位基因携带者(OR 18.5;95%CI 1.5 - 229;p = 0.023)。进一步分析显示ADRB2基因中的T - 47C、A46G、C79G和C491T(TACC)单倍型与TTN存在显著关联(p = 0.048)。

结论

我们得出结论,β1Gly49纯合性和ADRB2基因的TACC单倍型这两种功能丧失的基因变异可能易患TTN。

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