The CFTR K464N variant in fetuses potential increases premature birth risk in Chinese families

Abstract Background Global fertility decline has led to increased use of assisted reproductive technology (ART), raising concerns about genetic risks to offspring. This study aimed to investigate cystic fibrosis transmembrane conductance regulator (CFTR) variants in Chinese families and assess their...

Full description

Saved in:
Bibliographic Details
Main Authors: Jingping Li, Lingyun Zhang, Fangfang Xi, Chuanping Lin, Qitao Zhan, Qing Zhou, Shi Zheng, Weikang Chen, Fan Jin
Format: Article
Language:English
Published: BMC 2025-03-01
Series:Human Genomics
Online Access:https://doi.org/10.1186/s40246-025-00736-7
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849772402999820288
author Jingping Li
Lingyun Zhang
Fangfang Xi
Chuanping Lin
Qitao Zhan
Qing Zhou
Shi Zheng
Weikang Chen
Fan Jin
author_facet Jingping Li
Lingyun Zhang
Fangfang Xi
Chuanping Lin
Qitao Zhan
Qing Zhou
Shi Zheng
Weikang Chen
Fan Jin
author_sort Jingping Li
collection DOAJ
description Abstract Background Global fertility decline has led to increased use of assisted reproductive technology (ART), raising concerns about genetic risks to offspring. This study aimed to investigate cystic fibrosis transmembrane conductance regulator (CFTR) variants in Chinese families and assess their association with pregnancy complications and neonatal outcomes. Methods This prospective cohort study included 446 Chinese families (148 natural conceptions, 298 ART conceptions) who underwent whole genome sequencing. We analyzed the frequency of pathogenic/likely pathogenic CFTR variants and their association with preterm birth (PTB), pregnancy complications, and neonatal outcomes. Results Twelve pathogenic/likely pathogenic CFTR variants were identified, with K464N (c.1392G > T) being the most prevalent (2.9% of cohort). PTB incidence was significantly higher in pregnancies with fetal CFTR variants (43.1%, 22/51) compared to those without (17.5%, 69/395; p < 0.001). Fetuses carrying the CFTR K464N variant exhibited a 3.39-fold increased risk of PTB (95% confidence interval (CI): 1.39–8.23, p = 0.007) after adjusting for confounders. Neither fetal nor maternal CFTR variants were significantly associated with other neonatal outcomes, including neonatal weight, Apgar scores, respiratory distress, or hyperbilirubinemia (p > 0.050). Conclusion These findings suggest a potential association between fetal CFTR K464N variant and increased risk of preterm birth in Chinese families, highlighting the importance of considering CFTR genotyping in prenatal care.
format Article
id doaj-art-fe17c7e8b02f4930a2db3af10cacb22f
institution DOAJ
issn 1479-7364
language English
publishDate 2025-03-01
publisher BMC
record_format Article
series Human Genomics
spelling doaj-art-fe17c7e8b02f4930a2db3af10cacb22f2025-08-20T03:02:19ZengBMCHuman Genomics1479-73642025-03-0119111010.1186/s40246-025-00736-7The CFTR K464N variant in fetuses potential increases premature birth risk in Chinese familiesJingping Li0Lingyun Zhang1Fangfang Xi2Chuanping Lin3Qitao Zhan4Qing Zhou5Shi Zheng6Weikang Chen7Fan Jin8Department of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang UniversityDepartment of Obstetrics and Gynecology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical UniversityDepartment of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang UniversityDepartment of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang UniversityDepartment of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang UniversityBGl ResearchDepartment of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang UniversityDepartment of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang UniversityDepartment of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang UniversityAbstract Background Global fertility decline has led to increased use of assisted reproductive technology (ART), raising concerns about genetic risks to offspring. This study aimed to investigate cystic fibrosis transmembrane conductance regulator (CFTR) variants in Chinese families and assess their association with pregnancy complications and neonatal outcomes. Methods This prospective cohort study included 446 Chinese families (148 natural conceptions, 298 ART conceptions) who underwent whole genome sequencing. We analyzed the frequency of pathogenic/likely pathogenic CFTR variants and their association with preterm birth (PTB), pregnancy complications, and neonatal outcomes. Results Twelve pathogenic/likely pathogenic CFTR variants were identified, with K464N (c.1392G > T) being the most prevalent (2.9% of cohort). PTB incidence was significantly higher in pregnancies with fetal CFTR variants (43.1%, 22/51) compared to those without (17.5%, 69/395; p < 0.001). Fetuses carrying the CFTR K464N variant exhibited a 3.39-fold increased risk of PTB (95% confidence interval (CI): 1.39–8.23, p = 0.007) after adjusting for confounders. Neither fetal nor maternal CFTR variants were significantly associated with other neonatal outcomes, including neonatal weight, Apgar scores, respiratory distress, or hyperbilirubinemia (p > 0.050). Conclusion These findings suggest a potential association between fetal CFTR K464N variant and increased risk of preterm birth in Chinese families, highlighting the importance of considering CFTR genotyping in prenatal care.https://doi.org/10.1186/s40246-025-00736-7
spellingShingle Jingping Li
Lingyun Zhang
Fangfang Xi
Chuanping Lin
Qitao Zhan
Qing Zhou
Shi Zheng
Weikang Chen
Fan Jin
The CFTR K464N variant in fetuses potential increases premature birth risk in Chinese families
Human Genomics
title The CFTR K464N variant in fetuses potential increases premature birth risk in Chinese families
title_full The CFTR K464N variant in fetuses potential increases premature birth risk in Chinese families
title_fullStr The CFTR K464N variant in fetuses potential increases premature birth risk in Chinese families
title_full_unstemmed The CFTR K464N variant in fetuses potential increases premature birth risk in Chinese families
title_short The CFTR K464N variant in fetuses potential increases premature birth risk in Chinese families
title_sort cftr k464n variant in fetuses potential increases premature birth risk in chinese families
url https://doi.org/10.1186/s40246-025-00736-7
work_keys_str_mv AT jingpingli thecftrk464nvariantinfetusespotentialincreasesprematurebirthriskinchinesefamilies
AT lingyunzhang thecftrk464nvariantinfetusespotentialincreasesprematurebirthriskinchinesefamilies
AT fangfangxi thecftrk464nvariantinfetusespotentialincreasesprematurebirthriskinchinesefamilies
AT chuanpinglin thecftrk464nvariantinfetusespotentialincreasesprematurebirthriskinchinesefamilies
AT qitaozhan thecftrk464nvariantinfetusespotentialincreasesprematurebirthriskinchinesefamilies
AT qingzhou thecftrk464nvariantinfetusespotentialincreasesprematurebirthriskinchinesefamilies
AT shizheng thecftrk464nvariantinfetusespotentialincreasesprematurebirthriskinchinesefamilies
AT weikangchen thecftrk464nvariantinfetusespotentialincreasesprematurebirthriskinchinesefamilies
AT fanjin thecftrk464nvariantinfetusespotentialincreasesprematurebirthriskinchinesefamilies
AT jingpingli cftrk464nvariantinfetusespotentialincreasesprematurebirthriskinchinesefamilies
AT lingyunzhang cftrk464nvariantinfetusespotentialincreasesprematurebirthriskinchinesefamilies
AT fangfangxi cftrk464nvariantinfetusespotentialincreasesprematurebirthriskinchinesefamilies
AT chuanpinglin cftrk464nvariantinfetusespotentialincreasesprematurebirthriskinchinesefamilies
AT qitaozhan cftrk464nvariantinfetusespotentialincreasesprematurebirthriskinchinesefamilies
AT qingzhou cftrk464nvariantinfetusespotentialincreasesprematurebirthriskinchinesefamilies
AT shizheng cftrk464nvariantinfetusespotentialincreasesprematurebirthriskinchinesefamilies
AT weikangchen cftrk464nvariantinfetusespotentialincreasesprematurebirthriskinchinesefamilies
AT fanjin cftrk464nvariantinfetusespotentialincreasesprematurebirthriskinchinesefamilies