Objectives: This study aimed to explore the associations between soluble epoxide hydrolase 2 gene (EPHX2) variants and non-syndromic cleft lip with or without cleft palate (NSCL/P) in Chinese Han population.
Methods: We recruited 159 NSCL/P cases from Chinese Han population and carried out targeted resequencing using the whole genome sequencing data of 542 healthy Chinese individuals from Novegene internal database as controls. We classified EPHX2 variants as common or rare according to their minor allele frequency and performed an association analysis for common variations and a burden analysis for rare variations.
Results: The lowest P-value in NSCL/P was observed at rs57699806 (P=0.000 13, OR=2.849 and 95% CI: 1.691-4.800), followed by rs4732723 (P=0.006 50, OR=0.662 and 95%CI: 0.491-0.892), rs7829267 (P=0.009 20, OR=1.496 and 95%CI: 1.117-2.005), rs721619 (P=0.011 00, OR=1.474 and 95%CI: 1.098-1.980), and rs7816586 (P=0.040 00, OR=1.310 and 95%CI: 1.015-1.691). The odds ratios suggested the C allele at rs4732723 as a protective factor for NSCL/P and the reference alleles at other single nucleotide polymorphisms (SNPs) as the risk factors for NSCL/P. Burden analysis showed no statistical significance (P>0.05).
Conclusions: Through targeted resequencing, this study identified five SNPs named rs57699806, rs4732723, rs7829267, rs721619, and rs7816586 around the region of EPHX2 gene associated with NSCL/P in Chinese Han population. Four SNPs of rs57699806, rs4732723, rs7829267, and rs7816586 were first identified.
目的: 探究可溶性环氧化物水解酶2基因（EPHX2）的遗传变异位点与中国汉族人群非综合征型唇腭裂（NSCL/P）的相关性。方法: 本研究以159个中国汉族NSCL/P患者作为研究对象，对EPHX2基因区域开展了目标区域捕获测序，更全面地检测了EPHX2基因区域的遗传变异位点。以诺禾致源基因数据库的542名中国汉族健康人的全基因组测序数据作为对照，进行常见变异位点关联分析和针对罕见变异位点的负荷分析。结果: 在中国汉族人群NSCL/P的关联分析中发现，rs57699806的差异具有统计学意义（P=0.000 13，OR=2.849，95%CI：1.691~4.800），其次为rs4732723（P=0.006 50，OR=0.662，95%CI：0.491~0.892），rs7829267（P=0.009 20，OR=1.496，95%CI：1.117~2.005），rs721619（P=0.011 00，OR=1.474，95%CI：1.098~1.980）和rs7816586（P=0.040 00，OR=1.310，95%CI：1.015~1.691）。其中rs4732723的C等位基因可能具有保护作用，而其他4个单核苷酸多态性位点的参考等位基因均可能增加NSCL/P的发生风险。罕见变异负荷分析2组差异无统计学意义（P>0.05）。结论: 本研究发现，EPHX2基因的5个单核苷酸多态性位rs57699806、rs4732723、rs7829267、rs721619和rs7816586与中国汉族人群NSCL/P的发生密切相关，其中rs57699806、rs4732723、rs7829267和rs7816586为新发现的易感位点。.
Keywords: non-syndromic cleft lip with or without cleft palate; single nucleotide polymorphism; soluble epoxide hydrolase 2 gene; targeted resequencing.