巴西人群中单纯性唇裂伴或不伴腭裂易感性多态性分析。

Analysis of susceptibility polymorphisms for nonsyndromic cleft lip with or without cleft palate in the Brazilian population.

作者信息

de Aquino Sibele Nascimento, Messetti Ana Camila, Hoshi Ryuchi, Borges Andréa, Viena Camila Sane, Reis Sílvia R A, Oliveira Swerts Mário Sérgio, Graner Edgard, Martelli-Júnior Hercílio, Coletta Ricardo D

机构信息

Department of Oral Diagnosis, School of Dentistry, State University of Campinas, Piracicaba, São Paulo, Brazil.

出版信息

Birth Defects Res A Clin Mol Teratol. 2014 Jan;100(1):36-42. doi: 10.1002/bdra.23204.

DOI:10.1002/bdra.23204

PMID:24446087

Abstract

BACKGROUND

Although genome-wide association studies have identified several susceptibility loci for nonsyndromic cleft lip with or without cleft palate (NSCL/P) in populations around the world, the role of most loci is unknown in the highly heterogeneous Brazilian population.

METHODS

To determine the association of 7 markers that showed genome-wide significant association in Brazilians with NSCL/P, we conducted a structured association study conditioned upon the individual ancestry proportions to evaluate markers at 1p36 (rs742071), 2p21 (rs7590268), 3p11.1 (rs7632427), 8q21.3 (rs12543318), 13q31.1 (rs8001641), 15q22.2 (rs1873147), and 17q22 (rs227731) in 505 patients with NSCL/P and 594 healthy controls recruited from 2 different geographical regions of Brazil. The polymorphisms were genotyped by TaqMan 5'-exonuclease allelic discrimination assay, and each sample was independently typed for 40 biallelic short insertion/deletion markers to characterize the genomic ancestry.

RESULTS

After Bonferroni correction for multiple tests, significant associations with NSCL/P were observed for rs742071, rs1873147, and rs227731. However, the frequency of the risk alleles varied between the geographical regions, according to the proportions of European and African genomic ancestry. The group enriched by European ancestry showed significant association with rs227731 (p = 0.001), whereas the group with high African ancestry was significantly associated with rs1873147 polymorphism (p = 0.005). The significant association with rs742071 was only detected in the combined sample (p = 0.005).

CONCLUSION

The findings of the present study revealed the associations of 1p36 (rs742071), 15q22 (rs1873147), and 17p22 (rs227731) with NSCL/P in the Brazilian population, and further confirmed that the genetic heterogeneity of NSCL/P may be related to the different ethnic background of the affected individuals.

摘要

背景

尽管全基因组关联研究已经在世界各地人群中确定了几个非综合征性唇裂伴或不伴腭裂（NSCL/P）的易感基因座，但在高度异质的巴西人群中，大多数基因座的作用尚不清楚。

方法

为了确定在巴西人群中与NSCL/P呈现全基因组显著关联的7个标记物的关联性，我们进行了一项结构化关联研究，以个体祖先比例为条件，评估来自巴西2个不同地理区域招募的505例NSCL/P患者和594例健康对照中位于1p36（rs742071）、2p21（rs7590268）、3p11.1（rs7632427）、8q21.3（rs12543318）、13q31.1（rs8001641）、15q22.2（rs1873147）和17q22（rs227731）的标记物。通过TaqMan 5'-外切酶等位基因鉴别测定法对多态性进行基因分型，并且对每个样本独立检测40个双等位基因短插入/缺失标记物以表征基因组祖先。

结果

在对多重检验进行Bonferroni校正后，观察到rs742071、rs1873147和rs227731与NSCL/P存在显著关联。然而，根据欧洲和非洲基因组祖先的比例，风险等位基因的频率在不同地理区域之间有所不同。欧洲祖先富集的组与rs227731呈现显著关联（p = 0.001），而非洲祖先比例高的组与rs1873147多态性显著相关（p = 0.005）。仅在合并样本中检测到与rs742071的显著关联（p = 0.005）。