Sanchez-Dominguez Celia N, Reyes-Lopez Miguel A, Bustamante Adriana, Cerda-Flores Ricardo M, Villalobos-Torres Maria Del C, Gallardo-Blanco Hugo L, Rojas-Martinez Augusto, Martinez-Rodriguez Herminia G, Barrera-Saldaña Hugo A, Ortiz-Lopez Rocio
Departamento de Bioquimica y Medicina Molecular, Facultad de Medicina, Universidad Autonoma de Nuevo Leon, Monterrey, Nuevo Leon, Mexico.
Laboratorio de Medicina de Conservacion, Centro de Biotecnologia Genomica, Instituto Politecnico Nacional, Reynosa, Tamaulipas, Mexico.
PLoS One. 2014 Mar 6;9(3):e90945. doi: 10.1371/journal.pone.0090945. eCollection 2014.
Environmental and genetic factors may modify or contribute to the phenotypic differences observed in multigenic and monogenic diseases, such as cystic fibrosis (CF). An analysis of modifier genes can be helpful for estimating patient prognosis and directing preventive care. The aim of this study is to determine the association between seven genetic variants of four modifier genes and CF by comparing their corresponding allelic and genotypic frequencies in CF patients (n = 81) and control subjects (n = 104). Genetic variants of MBL2 exon 1 (A, B, C and D), the IL-8 promoter (-251 A/T), the TNFα promoter (TNF1/TNF2), and SERPINA1 (PIZ and PIS) were tested in CF patients and control subjects from northeastern Mexico by PCR-RFLP.
The TNF2 allele (P = 0.012, OR 3.43, 95% CI 1.25-9.38) was significantly associated with CF under the dominant and additive models but was not associated with CF under the recessive model. This association remained statistically significant after adjusting for multiple tests using the Bonferroni correction (P = 0.0482). The other tested variants and genotypes did not show any association with the disease.
An analysis of seven genetic variants of four modifier genes showed that one variant, the TNF2 allele, appears to be significantly associated with CF in Mexican patients.
环境和遗传因素可能会改变或导致在多基因和单基因疾病(如囊性纤维化,CF)中观察到的表型差异。对修饰基因的分析有助于评估患者预后并指导预防保健。本研究的目的是通过比较CF患者(n = 81)和对照受试者(n = 104)中四个修饰基因的七个遗传变异的相应等位基因和基因型频率,来确定它们与CF之间的关联。通过PCR-RFLP对来自墨西哥东北部的CF患者和对照受试者检测了MBL2外显子1(A、B、C和D)、IL-8启动子(-251 A/T)、TNFα启动子(TNF1/TNF2)和SERPINA1(PIZ和PIS)的遗传变异。
在显性和加性模型下,TNF2等位基因(P = 0.012,OR 3.43,95% CI 1.25 - 9.38)与CF显著相关,但在隐性模型下与CF不相关。使用Bonferroni校正进行多重检验校正后,这种关联仍具有统计学意义(P = 0.0482)。其他检测的变异和基因型与疾病无任何关联。
对四个修饰基因的七个遗传变异的分析表明,一个变异即TNF2等位基因,在墨西哥患者中似乎与CF显著相关。