Comparative analysis of common CFTR polymorphisms poly-T, TG-repeats and M470V in a healthy Chinese population

Abstract

Huang Q, Ding W, Wei MX. Comparative analysis of common CFTR polymorphisms poly-T, TG-repeats and M470V in a healthy Chinese population. World J Gastroenterol 2008; 14(12): 1925-1930 INTRODUCTIONThe cystic fibrosis transmembrane conductance regulator (CFTR) gene on chromosome 7q31 spans approximately 250 kb of DNA and encodes 27 exons encodes [1] . The CFTR gene encodes a cAMP-and ATP-dependent chloride channel that is present in the apical membrane of the epithelial cells that line most exocrine glands [2] . Phosphorylation of the regulatory domain by protein kinase A, followed by binding and hydrolysis of ATP at both nucleotide-binding domains, regulates the transport of chloride ions through the channel [3] . Absence, reduced levels, or malfunction of the CFTR protein results in cystic fibrosis (CF), and CF-like diseases such as congenital bilateral absence of the vas deferens (CBAVD) [4,5] , bronchiectasis [6] and chronic pancreatitis [7] . Since the discovery of the CFTR gene, more than 1000 mutations and 200 polymorphisms have been identified [8] . CF is one of the most common autosomal recessive disorders in Caucasians, with an incidence of approximately 1 in 2500 Caucasian births and a carrier frequency of approximately 1 in 25. However, in Asians, the prevalence of CF is very low, with an incidence of approximately 1 in 100 000, and in particular, the severe mutations, such as ∆F508, G542X and N1303K, are rarely found in Asians. Previous studies have demonstrated that polymorphisms outside the CFTR gene [9,10] , as well as within the gene, may affect transcription or function of the CFTR protein and modify the phenotype of some CF mutations. It has been mentioned that poly-T, TG-repeats and M470V polymorphisms play a role in the development of CF-like diseases. The poly-T tract located at the junction of intron Abstract AIM: To investigate the three important cystic fibrosis transmembrane conductance regulator (CFTR ) haplotypes poly-T, TG-repeats and the M470V polymorphisms in the Chinese population, and to compare their distribution with that in Caucasians and other Asian populations. RAPID COMMUNICATION METHODS:Genomic DNA was extracted from blood leukocytes. Exons 9 and 10 of the CFTR gene were obtained through polymerase chain reaction (PCR). Exon 9 DNA sequences were directly detected by an automated sequencer and poly-T and TG-repeats were identified by direct sequence analysis. Pure exon 10 PCRamplified products were digested by Hph Ⅰ restriction enzyme and the M470V mutation was detected by the AGE photos of digestion products.RESULTS: T7 was the most common (93.6%) haplotype and the (TG)11 frequency of 57.2% and (TG)12 frequency of 40.9% were dominant haplotypes in the junction of intron 8 (IVS-8) and exon 9. The frequency of T5 was 3.8% and all T5 allele tracts (10 alleles) were joined with (TG)12. Four new alleles of T6 (1.5%) were found in three healthy individuals. In exon 10, the V allele (56.1%) was slightly more frequent than the M allele (43.9%), and the M/V (45.5%) was the dominan...

The susceptibility of T5-TG12 of the CFTR gene in chronic bronchitis occurrence in a Chinese population in Jiangsu province, China

“…The results of the analysis of three previously determined polymorphic loci by frequency of alleles was consistent with previous reports of the frequencies of poly-T, TG-repeats, and M470V CFTR mutations in healthy Chinese populations[12]. These findings are also supported by a multitude of previous studies that suggest that while the frequency of these polymorphisms was quite different in the Caucasian populations, little variation was found in the East Asian populations[15]–[17].…”

“…Previous study has yielded critical information related to the polymorphism of poly-T, TG-repeats, and M470V in healthy Chinese populations[12]. In an effort to expand the scope of these observations, the present study was to investigate the specific impact of poly-T, TG-repeats, and M470V CFTR variations on susceptibility of a representative Chinese Han population in Jiangsu Province to bronchial asthma and chronic bronchitis.…”

Comprehensive screening for PRSS1, SPINK1, CFTR, CTRC and CLDN2 gene mutations in Chinese paediatric patients with idiopathic chronic pancreatitis: a cohort study

“…The TG repeats and poly-T tract can influence CFTR at transcription levels because these intronic variants could lead to reductions in protein synthesis and expression, or altered splicing to compromise the intracellular transport and/or activity. Huang et al 29 conducted the first comprehensive study on the functional polymorphisms of CFTR in Chinese healthy subjects and found that T7 was the most common haplotype (93.6%) and (TG)11 and (TG)12 were the dominant haplotypes in the junction of intron 8 and exon 9. Our current data also validated (TG)11-T7 as the most common type.…”

Poly Thymidine Polymorphism and Cystic Fibrosis in a Non-Caucasian Population

“…The T 7 allele is the most frequent in normal individuals with an approximate frequency of 80% in Caucasians [28,29] and 90% in East Asians [30]. However the frequency of poly T polymorphism in CF patients is controversial in different population studied.…”