Ekaterina Konstantinovna Zaikova, Aleksandra Vladimirovna Kaplina, Natalia Aleksandrovna Petrova, Tatiana Mikhailovna Pervunina, Anna Aleksandrovna Kostareva, Olga Viktorovna Kalinina
{"title":"患有先天性心脏缺陷和坏死性小肠结肠炎的足月新生儿中的 SIGIRR 基因变异。","authors":"Ekaterina Konstantinovna Zaikova, Aleksandra Vladimirovna Kaplina, Natalia Aleksandrovna Petrova, Tatiana Mikhailovna Pervunina, Anna Aleksandrovna Kostareva, Olga Viktorovna Kalinina","doi":"10.4103/apc.apc_30_23","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Necrotizing enterocolitis (NEC) is a common gastrointestinal emergency among neonates which is characterized by acute intestinal inflammation and necrosis. The main risk factors for NEC are prematurity, low birth weight, and some preexisting health conditions such as congenital heart defects (CHDs). Investigation of the potential genetic predisposition to NEC is a promising approach that might provide new insights into its pathogenesis. One of the most important proteins that play a significant role in the pathogenesis of NEC is Toll-like receptor 4 (TLR4) which recognizes lipopolysaccharide found in Gram-negative bacteria. In intestinal epithelial cells, a protein encoded by the <i>SIGIRR</i> gene is a major inhibitor of TLR4 signaling. A few <i>SIGIRR</i> variants, including rare p.Y168X and p.S80Y, have already been identified in preterm infants with NEC, but their pathogenic significance remains unclear. This study aimed to investigate the spectrum of <i>SIGIRR</i> genetic variants in term newborns with CHD and to assess their potential association with NEC.</p><p><strong>Methods and results: </strong>A total of 93 term newborns with critical CHD were enrolled in this study, 33 of them developed NEC. <i>SIGIRR</i> genetic variants were determined by Sanger sequencing of all exons. In total, eight <i>SIGIRR</i> genetic variants were identified, two of which were found only in newborns with NEC (<i>P</i> = 0.12). The rare missense p.S80Y (rs117739035) variant in exon 4 was found in two infants with NEC stage IIA. Two infants with NEC stage III and stage IB carried a novel duplication c. 102_121dup (rs552367848) variant in exon 10 that has not been previously associated with any clinical phenotype.</p><p><strong>Conclusions: </strong>The presence of both variants only in neonates who developed NEC, together with earlier published data, may suggest their potential contribution to the risk of developing NEC in term infants with CHD and allow planning larger cohort studies to clarify their relevance.</p>","PeriodicalId":8026,"journal":{"name":"Annals of Pediatric Cardiology","volume":null,"pages":null},"PeriodicalIF":0.9000,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11098289/pdf/","citationCount":"0","resultStr":"{\"title\":\"<i>SIGIRR</i> gene variants in term newborns with congenital heart defects and necrotizing enterocolitis.\",\"authors\":\"Ekaterina Konstantinovna Zaikova, Aleksandra Vladimirovna Kaplina, Natalia Aleksandrovna Petrova, Tatiana Mikhailovna Pervunina, Anna Aleksandrovna Kostareva, Olga Viktorovna Kalinina\",\"doi\":\"10.4103/apc.apc_30_23\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Necrotizing enterocolitis (NEC) is a common gastrointestinal emergency among neonates which is characterized by acute intestinal inflammation and necrosis. The main risk factors for NEC are prematurity, low birth weight, and some preexisting health conditions such as congenital heart defects (CHDs). Investigation of the potential genetic predisposition to NEC is a promising approach that might provide new insights into its pathogenesis. One of the most important proteins that play a significant role in the pathogenesis of NEC is Toll-like receptor 4 (TLR4) which recognizes lipopolysaccharide found in Gram-negative bacteria. In intestinal epithelial cells, a protein encoded by the <i>SIGIRR</i> gene is a major inhibitor of TLR4 signaling. A few <i>SIGIRR</i> variants, including rare p.Y168X and p.S80Y, have already been identified in preterm infants with NEC, but their pathogenic significance remains unclear. This study aimed to investigate the spectrum of <i>SIGIRR</i> genetic variants in term newborns with CHD and to assess their potential association with NEC.</p><p><strong>Methods and results: </strong>A total of 93 term newborns with critical CHD were enrolled in this study, 33 of them developed NEC. <i>SIGIRR</i> genetic variants were determined by Sanger sequencing of all exons. In total, eight <i>SIGIRR</i> genetic variants were identified, two of which were found only in newborns with NEC (<i>P</i> = 0.12). The rare missense p.S80Y (rs117739035) variant in exon 4 was found in two infants with NEC stage IIA. Two infants with NEC stage III and stage IB carried a novel duplication c. 102_121dup (rs552367848) variant in exon 10 that has not been previously associated with any clinical phenotype.</p><p><strong>Conclusions: </strong>The presence of both variants only in neonates who developed NEC, together with earlier published data, may suggest their potential contribution to the risk of developing NEC in term infants with CHD and allow planning larger cohort studies to clarify their relevance.</p>\",\"PeriodicalId\":8026,\"journal\":{\"name\":\"Annals of Pediatric Cardiology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.9000,\"publicationDate\":\"2023-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11098289/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of Pediatric Cardiology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.4103/apc.apc_30_23\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/4/1 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Pediatric Cardiology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.4103/apc.apc_30_23","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/4/1 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0
摘要
背景：坏死性小肠结肠炎（NEC坏死性小肠结肠炎（NEC）是新生儿常见的胃肠道急症，以急性肠道炎症和坏死为特征。发生 NEC 的主要风险因素是早产、出生体重过低以及一些原有的健康状况，如先天性心脏缺陷 (CHD)。对 NEC 潜在遗传易感性的研究是一种很有前景的方法，可能会为了解其发病机制提供新的视角。在 NEC 发病机制中起重要作用的最重要蛋白质之一是 Toll 样受体 4（TLR4），它能识别革兰氏阴性细菌中的脂多糖。在肠上皮细胞中，SIGIRR 基因编码的蛋白质是 TLR4 信号传导的主要抑制剂。在患有 NEC 的早产儿中已经发现了一些 SIGIRR 变异，包括罕见的 p.Y168X 和 p.S80Y，但其致病意义仍不清楚。本研究旨在调查患有先天性心脏病的足月新生儿的 SIGIRR 基因变异谱，并评估它们与 NEC 的潜在关联：本研究共纳入了 93 例患有严重先天性心脏病的足月新生儿，其中 33 例发生了 NEC。通过对所有外显子进行 Sanger 测序，确定了 SIGIRR 基因变异。总共发现了 8 个 SIGIRR 基因变异，其中 2 个变异仅在 NEC 新生儿中发现（P = 0.12）。在两个 NEC IIA 期的婴儿中发现了外显子 4 中的罕见错义 p.S80Y (rs117739035)变异。102_121dup (rs552367848)变异，该变异以前从未与任何临床表型相关联：结论：这两个变异仅存在于发生 NEC 的新生儿中，加上之前发表的数据，可能表明它们对患有先天性心脏病的足月儿发生 NEC 的风险有潜在影响，因此可以计划进行更大规模的队列研究，以明确它们的相关性。
SIGIRR gene variants in term newborns with congenital heart defects and necrotizing enterocolitis.
Background: Necrotizing enterocolitis (NEC) is a common gastrointestinal emergency among neonates which is characterized by acute intestinal inflammation and necrosis. The main risk factors for NEC are prematurity, low birth weight, and some preexisting health conditions such as congenital heart defects (CHDs). Investigation of the potential genetic predisposition to NEC is a promising approach that might provide new insights into its pathogenesis. One of the most important proteins that play a significant role in the pathogenesis of NEC is Toll-like receptor 4 (TLR4) which recognizes lipopolysaccharide found in Gram-negative bacteria. In intestinal epithelial cells, a protein encoded by the SIGIRR gene is a major inhibitor of TLR4 signaling. A few SIGIRR variants, including rare p.Y168X and p.S80Y, have already been identified in preterm infants with NEC, but their pathogenic significance remains unclear. This study aimed to investigate the spectrum of SIGIRR genetic variants in term newborns with CHD and to assess their potential association with NEC.
Methods and results: A total of 93 term newborns with critical CHD were enrolled in this study, 33 of them developed NEC. SIGIRR genetic variants were determined by Sanger sequencing of all exons. In total, eight SIGIRR genetic variants were identified, two of which were found only in newborns with NEC (P = 0.12). The rare missense p.S80Y (rs117739035) variant in exon 4 was found in two infants with NEC stage IIA. Two infants with NEC stage III and stage IB carried a novel duplication c. 102_121dup (rs552367848) variant in exon 10 that has not been previously associated with any clinical phenotype.
Conclusions: The presence of both variants only in neonates who developed NEC, together with earlier published data, may suggest their potential contribution to the risk of developing NEC in term infants with CHD and allow planning larger cohort studies to clarify their relevance.
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