Genetic Predisposition to Adverse Neurodevelopmental Outcome of Extremely Low Birth Weight Infants.

Autor:	Varner MW; Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, Utah., Thom EA; Biostatistics Coordinating Center, George Washington University, Washington, District of Columbia., Cotten CM; Department of Pediatrics, Duke University, Durham, North Carolina., Hintz SR; Department of Pediatrics, Stanford University School of Medicine and Lucile Packard Children's Hospital, Palo Alto, California., Page GP; Social, Statistical and Environmental Sciences Unit, RTI International, Atlanta, Georgia., Rouse DJ; Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, Alabama., Mercer BM; Case Western Reserve University-MetroHealth Medical Center, Cleveland, Ohio.; University of Tennessee, Memphis, Tennessee., Costantine MM; Department of Obstetrics and Gynecology, The Ohio State University, Columbus, Ohio., Sorokin Y; Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan., Thorp JM Jr; Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, North Carolina., Ramin SM; Department of Obstetrics and Gynecology, University of Texas Health Science Center at Houston-Children's Memorial Hermann Hospital, Houston, Texas., Carpenter MW; Department of Obstetrics and Gynecology, Brown University, Providence, Rhode Island., O'Sullivan MJ; Department of Obstetrics and Gynecology, University of Miami, Miami, Florida., Peaceman AM; Department of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois., Saade GR; Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas., Dudley DJ; Department of Obstetrics and Gynecology, University of Texas Health Sciences Center at San Antonio, San Antonio, Texas., Caritis SN; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania.
Jazyk:	angličtina
Zdroj:	American journal of perinatology [Am J Perinatol] 2024 May; Vol. 41 (S 01), pp. e2710-e2716. Date of Electronic Publication: 2023 Sep 19.
DOI:	10.1055/s-0043-1774312
Abstrakt:	Objective: This study aimed to evaluate whether there are genetic variants associated with adverse neurodevelopmental outcomes in extremely low birth weight (ELBW) infants. Study Design: We conducted a candidate gene association study in two well-defined cohorts of ELBW infants (<1,000 g). One cohort was for discovery and the other for replication. The discovery case-control analysis utilized anonymized DNA samples and evaluated 1,614 single-nucleotide polymorphisms (SNPs) in 145 genes concentrated in inflammation, angiogenesis, brain development, and oxidation pathways. Cases were children who died by age one or who were diagnosed with cerebral palsy (CP) or neurodevelopmental delay (Bayley II mental developmental index [MDI] or psychomotor developmental index [PDI] < 70) by 18 to 22 months. Controls were survivors with normal neurodevelopment. We assessed significant epidemiological variables and SNPs associated with the combined outcome of CP or death, CP, mental delay (MDI < 70) and motor delay (PDI < 70). Multivariable analyses adjusted for gestational age at birth, small for gestational age, sex, antenatal corticosteroids, multiple gestation, racial admixture, and multiple comparisons. SNPs associated with adverse neurodevelopmental outcomes with p  < 0.01 were selected for validation in the replication cohort. Successful replication was defined as p  < 0.05 in the replication cohort. Results: Of 1,013 infants analyzed (452 cases, 561 controls) in the discovery cohort, 917 were successfully genotyped for >90% of SNPs and passed quality metrics. After adjusting for covariates, 26 SNPs with p  < 0.01 for one or more outcomes were selected for replication cohort validation, which included 362 infants (170 cases and 192 controls). A variant in SERPINE1, which encodes plasminogen activator inhibitor (PAI1), was associated with the combined outcome of CP or death in the discovery analysis ( p  = 4.1 × 10 -4 ) and was significantly associated with CP or death in the replication cohort (adjusted odd ratio: 0.4; 95% confidence interval: 0.2-1.0; p  = 0.039). Conclusion: A genetic variant in SERPINE1, involved in inflammation and coagulation, is associated with CP or death among ELBW infants. Key Points: · Early preterm and ELBW infants have dramatically increased risks of CP and developmental delay.. · A genetic variant in SERPINE1 is associated with CP or death among ELBW infants.. · The SERPINE1 gene encodes the serine protease inhibitor plasminogen activator inhibitor.. Competing Interests: None declared. (Thieme. All rights reserved.)
Databáze:	MEDLINE
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