Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.
PLoS One. 2012;7(4):e35347. doi: 10.1371/journal.pone.0035347. Epub 2012 Apr 13.
The Bone Morphogenetic Protein 4 gene (BMP4) is located in chromosome 14q22-q23 which has shown evidence of linkage for isolated nonsyndromic cleft lip with or without cleft palate (NSCL/P) in a genome wide linkage analysis of human multiplex families. BMP4 has been shown to play crucial roles in lip and palatal development in animal models. Several candidate gene association analyses also supported its potential risk for NSCL/P, however, results across these association studies have been inconsistent. The aim of the current study was to test for possible association between markers in and around the BMP4 gene and NSCL/P in Asian and Maryland trios.
METHODOLOGY/PRINCIPAL FINDINGS: Family Based Association Test was used to test for deviation from Mendelian assortment for 12 SNPs in and around BMP4. Nominal significant evidence of linkage and association was seen for three SNPs (rs10130587, rs2738265 and rs2761887) in 221 Asian trios and for one SNP (rs762642) in 76 Maryland trios. Statistical significance still held for rs10130587 after Bonferroni correction (corrected p = 0.019) among the Asian group. Estimated odds ratio for carrying the apparent high risk allele at this SNP was 1.61 (95%CI = 1.20, 2.18).
Our results provided further evidence of association between BMP4 and NSCL/P.
骨形态发生蛋白 4 基因(BMP4)位于染色体 14q22-q23,在人类多病例家系的全基因组连锁分析中,该基因显示出与孤立性非综合征性唇裂伴或不伴腭裂(NSCL/P)的连锁证据。在动物模型中,BMP4 已被证明在唇和腭的发育中起着关键作用。几项候选基因关联分析也支持其对 NSCL/P 的潜在风险,但这些关联研究的结果并不一致。本研究的目的是检测 BMP4 基因内和周围的标记物与亚洲和马里兰州三病例组中 NSCL/P 之间是否存在关联。
方法/主要发现:使用基于家庭的关联测试来检测 12 个 BMP4 基因内和周围的 SNP 是否符合孟德尔分离。在 221 个亚洲三病例组中,有三个 SNP(rs10130587、rs2738265 和 rs2761887)和一个 SNP(rs762642)在马里兰州三病例组中出现了名义上显著的连锁和关联证据。在亚洲组中,经过 Bonferroni 校正后,rs10130587 仍具有统计学意义(校正后 p=0.019)。该 SNP 上携带明显高风险等位基因的估计优势比为 1.61(95%CI=1.20,2.18)。
我们的研究结果为 BMP4 与 NSCL/P 之间的关联提供了进一步的证据。