Beaty Terri H, Hetmanski J B, Zeiger J S, Fan Y T, Liang K Y, VanderKolk C A, McIntosh I
Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA.
Genet Epidemiol. 2002 Jan;22(1):1-11. doi: 10.1002/gepi.1039.
Markers in five candidate genes were examined on 269 case-parent trios ascertained through a child with an isolated, non-syndromic oral cleft (cleft lip, CL; cleft palate, CP; or cleft lip and palate, CLP). Cases and their parents were ascertained through treatment centers in Maryland. Markers at two of the five candidate genes, transforming growth factor beta3 (TGFbeta3) and MSX1, showed consistent evidence of linkage and disequilibrium due to linkage using several statistical tests (e.g., the global chi-square for TGFbeta3 was 21.1 with 12 df, P = 0.03; that for MSX1 was 8.7 with 3 df, P = 0.03). There was little evidence of heterogeneity in the role of TGFbeta3 between different types of oral clefts, but MSX1 did yield marginal evidence for such heterogeneity. MSX1 also showed evidence for interaction between infant's genotype and maternal smoking, giving a likelihood ratio test for heterogeneity between smoker and non-smoker mothers of 7.16 (2 df, P = 0.03). Using a conditional logistic model to test for gene-gene interaction showed no evidence of interaction between TGFbeta3 and MSX1, with both seeming to contribute independently to risk of isolated, non-syndromic oral clefts.
在269个病例-父母三联体中检测了五个候选基因的标记物，这些三联体是通过患有孤立性、非综合征性口腔裂隙（唇裂，CL；腭裂，CP；或唇腭裂，CLP）的儿童确定的。病例及其父母是通过马里兰州的治疗中心确定的。在五个候选基因中的两个基因，即转化生长因子β3（TGFbeta3）和MSX1上的标记物，通过几种统计检验（例如，TGFbeta3的全局卡方值为21.1，自由度为12，P = 0.03；MSX1的全局卡方值为8.7，自由度为3，P = 0.03）显示出由于连锁而产生的一致的连锁和不平衡证据。在不同类型的口腔裂隙之间，TGFbeta3的作用几乎没有异质性的证据，但MSX1确实产生了这种异质性的边缘证据。MSX1还显示出婴儿基因型与母亲吸烟之间存在相互作用的证据，吸烟者和非吸烟者母亲之间的异质性似然比检验为7.16（自由度为2，P = 0.03）。使用条件逻辑模型来检验基因-基因相互作用，未显示TGFbeta3和MSX1之间存在相互作用的证据，两者似乎独立地对孤立性、非综合征性口腔裂隙的风险有贡献。
