جستجوی مقالات مرتبط با کلیدواژه « cftr » در نشریات گروه « پزشکی »

Studies have revealed a strong association between mutations of CFTR gene and the congenital bilateral absence of the vas deferens (CBAVD), but the role of this gene in other types of male infertility is still unclear. The purpose of this study was to investigate the frequency of the most common mutations of the CFTR gene (DF508, G542X, N1303K, G551D, and W1282X) in a population of infertile men with nonobstructive azoospermia (NOA) and CBAVD in Iran. Blood samples were obtained from 50 NOA, 50 CBAVD, and 100 normal males (control). Genomic DNA was isolated from whole blood leukocytes, and the presence of common mutations of the CFTR gene was assessed by an amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Restriction fragment length polymorphism (PCR-RFLP) was also used to analyze IVS8-Tn polymorphism. It was found that 16%, 8%, and 8% of patients with CBAVD were heterozygote for DF508, G542X, and N1303K, respectively. The frequency of the 5T allele was 34% and higher than the normal group (p < 0.001). None of the common CFTR gene mutations were detected in NOA patients, and no significant difference was found in the distribution of the 5T allele between the NOA patients and the control group (5 vs. 3 p = 0.721). Based on the present case-control study, the CFTR gene mutations and IVS8-Tn polymorphisms are correlated with CBAVD; however, extensive investigations are necessary to determine the exact relationship between the gene mutations and other forms of male infertility.

Cystic fibrosis (CF) is a common genetic disorder in white populations with an autosomal recessive pattern, caused by mutations in the CFTR gene. The frequency of more than 1950 various mutations reported in the CFTR gene significantly varies in different populations. ∆F508 is a common mutation in exon 10, which is first addressed in the molecular analysis of the disease. Other exons are required to be investigated owing to failing to identify mutations in the patients. The present study was conducted to investigate mutations in exons 4, 11 and 21 of the CFTR gene using the sequencing method in CF patients in Kermanshah province, Iran.
The present descriptive study was conducted on all patients with CF presenting to the medical genetics center in Kermanshah in 2010-2011. After taking blood samples and extracting DNA using saturated NaCl solution, sequences of exons were amplified using PCR and sequenced for identifying mutations.
The frequency of mutations was found to be respectively 0, 0 and 5.5% in exon 11, 21 and 4. The D110H mutation was found to be homozygous in one subject and heterozygous in another. Moreover, the 4029A>G polymorphism (12.9%) was found to be homozygous in two subjects and heterozygous in three others.
The D110H mutation is recommended to be included in the screening programs of the study population. The results obtained support the effects of ethnic and geographical factors on the distribution of CF mutations.

The cystic fibrosis transmembrane conductance regulator (CFTR) chloride (Cl−) channel is an essential component of epithelial Cl− transport systems in many organs. CFTR is mainly expressed in the lung and other tissues, such as testis, duodenum, trachea and kidney. The ubiquitin ligase neural precursor cells expressed developmentally down-regulated protein 4-2 (Nedd4-2) has previously been shown to regulate abundance of several channel and carrier proteins in the plasma membrane, an effect reversed by glucocorticoid dependent kinase 1 (SGK1).
The present study was thus performed to elucidate the sensitivity of CFTR to regulation by Nedd4-2 and the serum and SGK1. To this end, the CFTR was heterologously expressed in oocytes alone or together with Nedd4-2 or the SGK1. The cRNAs encoding CFTR, Nedd4-2 and/or the constitutively active S422DSGK1 have been injected into Xenopus oocytes. The activity of CFTR was measured by the two-electrode voltage-clamp technique and CFTR-mediated currents were elicited by the application of forskolin and IBMX (F/I).
As a result, forskolin/IBMX treatment triggered cAMP-stimulated ion currents (IcAMP) in Xenopus oocytes expressing CFTR cRNA, but not in oocytes injected with water (control). Co-expression of Nedd4-2 markedly down-regulates the cAMP-stimulated ion current (IcAMP), an effect reversed by Co-expression of the constitutively active S422DSGK1. In Xenopus oocytes co-expressing CFTR with S422DSGK1 the cAMP-stimulated ion current (IcAMP) was similar to that in Xenopus oocytes expressing CFTR alone.
The present observations suggest that CFTR is a target for the ubiquitin ligase Nedd4-2, which is inactivated by the SGK1.

The genetic association between cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and male infertility due to congenital bilateral absence of vas deferens (CBAVD) is well established. Mutant CFTR, however may also be involved in the etiology of male infertility in non-CBAVD cases. The present study was conducted to estimate the frequency of ∆I507 and ∆F508 CFTR gene mutations in Iranian infertile males. We undertook the first study of association between these CFTR mutations and non-obstructive azoospermia in Iran. In this case-control study, 100 fertile healthy fathers and 100 non-obstructive azoospermia’s men were recruited from Isfahan Infertility Center (IIC) and Sari Saint Mary’s Infertility Center, between 2008 and 2009. Screening of F508del and I507del mutations was carried out by the multiplex-ARMS-PCR. Significance of differences in mutation frequencies between the patient and control groups was assessed by Fisher’s exact test. The ΔF508 was detected in three patients. However there are no significant association was found between the presence of this mutated allele and infertility [OR=9.2 (allele-based) and 7.2 (individual-based), P=0.179]. None of the samples carried the ΔI507 mutation. Altogether, we show that neither ΔI507 nor ΔF508 is involved in this population of Iranian infertile males with non-obstructive azoospermia.