Журнал генетических синдромов и генной терапии
Открытый доступ

Абстрактный

ADIPOR2 Polymorphisms in Cystic Fibrosis are Potential Modifiers of Clinical Severity

Fernando Augusto de Lima Marson, Luiza Annelene Zimmermann, Jose Dirceu Ribeiro and Carmen Silvia Bertuzzo

Objective: Cystic Fibrosis (CF) severity is determined by mutations in the Cystic Fibrosis Transmembrane Regulator (CFTR) gene, the environment and modifier genes. The adiponectin receptor 2 (ADIPOR2) gene is one of the potential modifier genes of CF and is responsible for expressing an anti-inflammatory protein. In this context, the 315 base deletion and the 134 base insertion polymorphisms in the ADIPOR2 gene are associated with CF severity. Methodology: A total of 169 CF patients were enrolled, and 27 CF clinical markers were analyzed. Results: The 315 base deletion and haplotypes analyses showed an association with the patient´s age and ethnicity. For the age, the deletion in both alleles was associated with a lower age in the patients without any identified CFTR mutations (OR= 7.257; 95%CI= 1.321-44.83) or disregarding CFTR mutations (OR= 2.394; 95%CI= 1.046- 5.721). For the ethnicity, the wild-type allele (315 base no deletion) showed lower risk of occurrence in Caucasians patients with two CFTR mutations identified (OR= 0.052; 95%CI= 0.002-0.382) or no CFTR mutations (OR= 0.154, 95%CI= 0.032-0.592). The same values were observed for the clustered analysis of the 315 base deletions. In the analysis of the haplotype, in the Caucasian group, the patients with two CFTR mutations were identified and demonstrated an OR of 0.076 (95%CI= 0.009-0.432) for wild-type alleles. The 134 base insertions were associated with the SpO2 [patients without considering the CFTR genotype (p-value= 0.034) and without any identified CFTR mutations (p-value= 0.034)] and the Kanga score (no CFTR mutations identified) (p-value= 0.008). The haplotype was associated with the forced vital capacity (disregarding CFTR genotype) (p-value= 0.028). Conclusion: The 315 base deletions and the insertion of 134 bases in the ADIPOR2 gene are potential modifiers of the severity of CF and should be considered during CFTR mutation screening.