中国新疆维吾尔族人群中CRISPLD2基因与非综合征性唇腭裂（nsCL/P）之间相互作用的初步证据。

Preliminary evidence of an interaction between the CRISPLD2 gene and non-syndromic cleft lip with or without cleft palate (nsCL/P) in Xinjiang Uyghur population, China.

作者信息

Mijiti Ainiwaer, Ling Wang, Maimaiti Abudukelimujiang, Tuerdi Maimaitituxun, Tuerxun Julaiti, Moming Adili

机构信息

Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Xinjiang Medical University, No.137 South Li YU-shan Road, New City District 830054 Urumqi, Xinjiang, PR China; Stomatological Research Institute of Xinjiang Uyghur Autonomous Region, Urumqi, Xinjiang 830054, PR China.

出版信息

Int J Pediatr Otorhinolaryngol. 2015 Feb;79(2):94-100. doi: 10.1016/j.ijporl.2014.10.043. Epub 2014 Nov 11.

DOI:10.1016/j.ijporl.2014.10.043

PMID:25496823

Abstract

BACKGROUND

Non-syndromic cleft lip with or without cleft palate (nsCL/P) is a common birth defect results from the genetic factors alone or interactions with environmental changes. Single nucleotide polymorphisms (SNPs) of CRISPLD2 gene have been found to be an etiologic factor in the development of nsCL/P. However, few studies to date focused on the association of genetic variation of CRISPLD2 gene with nsCL/P, and the results are conflicting based on the different study population. The main purpose of the present study was to investigate the association between the CRISPLD2 gene and nsCL/P in Xinjiang Uyghur population.

METHODS

Eighteen SNPs were screened in a group of 200 patients with nsCL/P and in a control group consisting of 180 unaffected individuals by next generation sequencing using MiSeq Benchtop Sequencer (Illumina).

RESULTS

Our case-control association analysis showed that the SNP marker rs1546124 showed statistically significant differences in genotype (CC vs. CG vs. GG P=0.004) and allele frequencies (49% vs. 37.8% OR=1.58; 95% CI=1.19-2.1, P=0.002) between nsCL/P and controls. Under the recessive model of inheritance, the GG homozygotes had an OR of 2.4 (95% CI=1.37-4.18; P=0.002), and the result of significance was maintained even after multiple testing correction. Haplotype combinations of CACC were significantly more frequent in the nsCL/P patients than in controls (P=0.037). Finally, the MDR analysis identified the two-SNP model including rs1546124 and rs4782675 as best combination of possibly interactive polymorphisms (P<0.001).

CONCLUSION

Our results demonstrate that genetic polymorphism of CRISPLD2 gene is associated with an increased risk of nsCL/P in a Xinjiang Uyghur population.

摘要

背景

非综合征性唇裂伴或不伴腭裂（nsCL/P）是一种常见的出生缺陷，其由单独的遗传因素或与环境变化的相互作用导致。已发现CRISPLD2基因的单核苷酸多态性（SNP）是nsCL/P发生发展的一个病因学因素。然而，迄今为止，很少有研究关注CRISPLD2基因的遗传变异与nsCL/P的关联，并且基于不同的研究人群，结果相互矛盾。本研究的主要目的是调查新疆维吾尔族人群中CRISPLD2基因与nsCL/P之间的关联。

方法

使用MiSeq台式测序仪（Illumina）通过下一代测序在一组200例nsCL/P患者和由180名未受影响个体组成的对照组中筛选了18个SNP。

结果

我们的病例对照关联分析表明，SNP标记rs1546124在nsCL/P患者和对照组之间的基因型（CC与CG与GG，P = 0.004）和等位基因频率（49%对37.8%，OR = 1.58；95%CI = 1.19 - 2.1，P = 0.002）上显示出统计学上的显著差异。在隐性遗传模式下，GG纯合子的OR为2.4（95%CI = 1.37 - 4.18；P = 0.002），即使在多重检验校正后，显著性结果仍然成立。CACC的单倍型组合在nsCL/P患者中比在对照组中显著更频繁（P = 0.037）。最后，MDR分析确定包括rs1546124和rs4782675的双SNP模型为可能相互作用的多态性的最佳组合（P < 0.001）。