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慢性胰腺炎中与不良妊娠结局相关的遗传因素

Genetic Factors Associated With Adverse Pregnancy Outcomes in Chronic Pancreatitis.

作者信息

Wu Di, Ru Nan, Wang Yuan-Chen, Ma Guo-Xiu, Shi Tian-Yu, Xiong Si-Huai, You Ai-Jun, Wang Lei, Hu Liang-Hao, Li Zhao-Shen, Zou Wen-Bin, Liao Zhuan

机构信息

Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China.

Shanghai Institute of Pancreatic Diseases, Shanghai, China.

出版信息

Clin Transl Gastroenterol. 2024 Apr 1;15(4):e00691. doi: 10.14309/ctg.0000000000000691.

Abstract

INTRODUCTION

The effects of genetic factors on pregnancy outcomes in chronic pancreatitis (CP) patients remain unclear. We evaluated the impacts of clinical features and mutations in main CP-susceptibility genes ( SPINK1 , PRSS1 , CTRC , and CFTR ) on pregnancy outcomes in Chinese CP patients.

METHODS

This was a prospective cohort study with 14-year follow-up. The sample comprised female CP patients with documented pregnancy and known genetic backgrounds. Adverse pregnancy outcomes were compared between patients with and without gene mutations. Univariate and multivariate analyses were performed to determine the impact factors for adverse pregnancy outcomes.

RESULTS

Totally, 160 female CP patients with a pregnancy history were enrolled; 59.4% of patients carried pathogenic mutations in CP-susceptibility genes. Adverse pregnancy outcomes occurred in 38 patients (23.8%); the prevalence of adverse outcomes was significantly higher in those harboring gene mutations than those without (30.5% vs 13.8%, P = 0.015). Notably, the rates of preterm delivery (12.6% vs 3.1%, P = 0.036) and abortion (17.9% vs 4.6%, P = 0.013) were remarkably higher in patients with gene mutations (especially SPINK1 mutations) than those without. In multivariate analyses, both CP-susceptibility gene mutations (odds ratio, 2.52; P = 0.033) and SPINK1 mutations (odds ratio, 2.60; P = 0.037) significantly increased the risk of adverse pregnancy outcomes. Acute pain attack during pregnancy was another risk factor for adverse pregnancy outcomes.

DISCUSSION

Pathogenic mutations in CP-susceptibility genes, especially SPINK1 , were independently related to adverse pregnancy outcomes in CP patients. Significant attention should be paid to pregnant females harboring CP-susceptibility gene mutations (ClinicalTrials.gov: NCT06055595).

摘要

引言

遗传因素对慢性胰腺炎(CP)患者妊娠结局的影响尚不清楚。我们评估了临床特征以及主要CP易感基因(SPINK1、PRSS1、CTRC和CFTR)突变对中国CP患者妊娠结局的影响。

方法

这是一项为期14年随访的前瞻性队列研究。样本包括有妊娠记录且已知遗传背景的女性CP患者。比较了有基因突变和无基因突变患者的不良妊娠结局。进行单因素和多因素分析以确定不良妊娠结局的影响因素。

结果

共纳入160例有妊娠史的女性CP患者;59.4%的患者携带CP易感基因的致病突变。38例患者(23.8%)出现不良妊娠结局;有基因突变患者的不良结局发生率显著高于无基因突变患者(30.5%对13.8%,P = 0.015)。值得注意的是,有基因突变(尤其是SPINK1突变)的患者早产率(12.6%对3.1%,P = 0.036)和流产率(17.9%对4.6%,P = 0.013)明显高于无基因突变患者。在多因素分析中,CP易感基因突变(比值比,2.52;P = 0.033)和SPINK1突变(比值比,2.60;P = 0.037)均显著增加不良妊娠结局的风险。孕期急性疼痛发作是不良妊娠结局的另一个危险因素。

讨论

CP易感基因的致病突变,尤其是SPINK1,与CP患者的不良妊娠结局独立相关。应高度关注携带CP易感基因突变的妊娠女性(ClinicalTrials.gov:NCT06055595)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adca/11042769/3e078422e594/ct9-15-e00691-g001.jpg

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