Cystic fibrosis transmembrane regulator haplotypes in households of patients with cystic fibrosis.

INTRODUCTION: Nearly 2000 mutations in the cystic fibrosis transmembrane regulator (CFTR) gene have been reported. The F508del mutation occurs in approximately 50-65% of patients with cystic fibrosis (CF). However, molecular diagnosis is not always possible. Therefore, silent polymorphisms can be used to label the mutant allele in households of patients with CF. OBJECTIVE: To verify the haplotypes of four polymorphisms at the CFTR locus in households of patients with CF for pre-fertilization, pre-implantation, and prenatal indirect mutation diagnosis to provide better genetic counseling for families and patients with CF and to associate the genotypes/haplotypes with the F508del mutation screening. METHODS: GATT polymorphism analysis was performed using direct polymerase chain reaction amplification, and the MP6-D9, TUB09 and TUB18 polymorphism analyses were performed using restriction fragment length polymorphism. RESULTS: Nine haplotypes were found in 37 CFTR alleles, and of those, 24 were linked with the F508del mutation and 13 with other CFTR mutations. The 6 (GATT), C (MP6-D9), G (TUB09), and C (TUB18) haplotypes showed the highest prevalence (48%) of the mutant CFTR allele and were linked to the F508del mutation (64%). In 43% of households analyzed, at least one informative polymorphism can be used for the indirect diagnostic test. CONCLUSION: CFTR polymorphisms are genetic markers that are useful for identifying the mutant CFTR alleles in households of patients with CF when it is not possible to establish the complete CFTR genotype. Moreover, the polymorphisms can be used for indirect CFTR mutation identification in cases of pre-fertilization, pre-implantation and prenatal analysis.

Association between the IVS4G>T mutation in the TCF7L2 gene and susceptibility to diabetes in cystic fibrosis patients.

BACKGROUND: Clinical complications appear to be a decisive factor for the prognosis of patients. Diabetes is an important complication of cystic fibrosis(CF). In our study we evaluated the association between the IVS4G>T mutation in the TCF7L2 gene with the presence of diabetes in patients with CF. FINDINGS: We evaluated 145 patients with CF in relation to the genotype of the IVS4G>T mutation. For this, the PCR method associated with specific enzyme digestion was used. The genotypes G/G, G/T and T/T were observed to have frequencies of 54 (37.2%), 78 (53.8%) and 13 (9%), respectively. There was no association between genotype and the occurrence of diabetes among patients. CONCLUSIONS: In our sample, no association was found between the IVS4G>T mutation in the TCF7L2 gene and diabetes.