Association between CpG-SNPs and nonsyndromic cleft lip palate in a Chilean population

IF 2.1 4区医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE

Archives of oral biology Pub Date : 2025-07-19 DOI:10.1016/j.archoralbio.2025.106358

Patricio González-Hormazábal , Noemí Leiva , Rosa Pardo , José Suazo

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引用次数: 0

Abstract

Objective

To assess the association between common variants in CpG islands (CpG-SNPs) related to the expression of selected genes, and the risk of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in a Chilean sample.

Design

A total of 239 Chilean NSCL/P unrelated cases and 524 controls were genotyped using GSA array. Genotypes were imputed from the array, selecting those located within CpG islands coordinates and associated with the expression of genes differentially expressed in human cleft tissues. These selected SNPs were used for association analysis with NSCL/P based on logistic regression.

Results

A total of 96 CpG-SNP met the above-mentioned criteria. After multiple comparisons correction (p-value<0.000862), only rs12940418 remains significantly associated with NSCL/P (OR 0.644, 95 % CI 0.496–0.833, p-value=0.000859). Although this variant is located 540 Kb away from the transcription start site of SHMT1, it has evidence of modulating its expression.

Conclusions

The most plausible biological explanation for our results is cis/distal regulatory effect of rs12940418 on the expression of SHMT1. This gene encodes an enzyme implicated in folate/one-carbon metabolism, and its variants have been previously associated with NSCL/P in our population. Our results reveal the role of epigenetic mechanisms in birth defects expression such as DNA methylation and small RNAs.

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智利人群中cpg - snp与非综合征性唇腭裂的关系

目的评估智利CpG岛常见基因变异（CpG- snp）与特定基因表达与非综合征性唇裂伴或不伴腭裂（NSCL/P）风险的关系。239例智利NSCL/P非相关病例和524例对照采用GSA基因分型。从该阵列中选择位于CpG岛坐标内且与人裂组织中差异表达基因表达相关的基因型进行基因型估算。这些选择的snp用于基于逻辑回归的NSCL/P相关性分析。结果共有96个CpG-SNP符合上述标准。经多次比较校正（P值<；0.000862），只有rs12940418与NSCL/P显著相关（OR 0.644, 95 % CI 0.496-0.833， P值=0.000859）。尽管该变异位于距SHMT1转录起始位点540 Kb处，但有证据表明它可以调节SHMT1的表达。结论rs12940418对SHMT1表达的顺式/远端调控是本研究结果最合理的生物学解释。该基因编码一种与叶酸/单碳代谢有关的酶，其变体先前与我们人群中的nsl /P有关。我们的研究结果揭示了表观遗传机制在出生缺陷表达中的作用，如DNA甲基化和小rna。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Archives of oral biology 医学-牙科与口腔外科

CiteScore

5.10

自引率

3.30%

发文量

177

审稿时长

26 days

期刊介绍： Archives of Oral Biology is an international journal which aims to publish papers of the highest scientific quality in the oral and craniofacial sciences. The journal is particularly interested in research which advances knowledge in the mechanisms of craniofacial development and disease, including: Cell and molecular biology Molecular genetics Immunology Pathogenesis Cellular microbiology Embryology Syndromology Forensic dentistry