Are Immune Modulating Single Nucleotide Polymorphisms Associated with Necrotizing Enterocolitis?
Are Immune Modulating Single Nucleotide Polymorphisms Associated with Necrotizing Enterocolitis?
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DOI：
10.1038/srep18369
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发表时间：
2015-12-16
影响因子：
4.6
通讯作者：
Sandler, Anthony D.
中科院分区：
文献类型：
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作者：
Franklin, Ashanti L.;Said, Mariam;Sandler, Anthony D.
坏死性小肠结肠炎（NEC）是一种毁灭性的胃肠道急症。本研究的目的是确定免疫调节基因的功能性单核苷酸多态性（SNPs）是否易患NEC。在机构审查委员会批准和父母同意后，收集口腔拭子用于DNA提取。使用TaqMan等位基因区分测定和BglII内切核酸酶消化对特异性炎性细胞因子和TRIM 21进行基因分型。使用逻辑回归完成统计分析。184名新生儿在研究中进行了分析。携带IL-6（rs 1800795）的白人新生儿发生NEC的可能性高6倍以上（p = 0.013; OR = 6.61，95% CI 1.48-29.39），发生III期疾病的可能性高7倍以上（p = 0.011; OR = 7.13，（95% CI 1.56-32.52）。TGF β-1（rs 2241712）新生儿的NEC相关穿孔发生率降低（p = 0.044; OR = 0.28，95% CI：0.08-0.97），死亡率增加（p = 0.049; OR = 2.99，95% CI：1.01 - 8.86）。TRIM 21（rs660）与NEC相关的肠穿孔相关（p = 0.038; OR = 4.65，95% CI 1.09-19.78）。在早产白人新生儿中，功能性SNP IL-6（rs 1800795）与NEC的发展和严重程度增加相关。TRIM 21（rs660）和TGF β-1（rs 2241712）与队列中所有新生儿的NEC相关穿孔相关。这些发现表明NEC的发展中可能的遗传作用。
Necrotizing enterocolitis (NEC) is a devastating gastrointestinal emergency. The purpose of this study is to determine if functional single nucleotide polymorphisms (SNPs) in immune-modulating genes pre-dispose infants to NEC. After Institutional Review Board approval and parental consent, buccal swabs were collected for DNA extraction. TaqMan allelic discrimination assays and BglII endonuclease digestion were used to genotype specific inflammatory cytokines and TRIM21. Statistical analysis was completed using logistic regression. 184 neonates were analyzed in the study. Caucasian neonates with IL-6 (rs1800795) were over 6 times more likely to have NEC (p = 0.013; OR = 6.61, 95% CI 1.48-29.39), and over 7 times more likely to have Stage III disease (p = 0.011; OR = 7.13, (95% CI 1.56-32.52). Neonates with TGF beta-1 (rs2241712) had a decreased incidence of NEC-related perforation (p = 0.044; OR = 0.28, 95% CI: 0.08-0.97) and an increased incidence of mortality (p = 0.049; OR = 2.99, 95% CI: 1.01 -8.86). TRIM21 (rs660) was associated with NEC-related intestinal perforation (p = 0.038; OR = 4.65, 95% CI 1.09-19.78). In premature Caucasian neonates, the functional SNP IL-6 (rs1800795) is associated with both the development and increased severity of NEC. TRIM21 (rs660) and TGF beta-1 (rs2241712) were associated with NEC-related perforation in all neonates in the cohort. These findings suggest a possible genetic role in the development of NEC.