Results found: 3

Number of results on page

Search results

Search:
in the keywords: GENOTYPE-PHENOTYPE CORRELATION

Sort By:

Limit search:

Modifier effect of the Toll-like receptor 4 D299G polymorphism in children with cystic fibrosis

100%

Urquhart D. S., Allen J., Elrayess M., Fidler K., Klein N., Jaffe A.

Archivum Immunologiae et Therapiae Experimentalis

2006

vol. 54

issue 4

271-276

Introduction: Clinical phenotype varies amongst cystic fibrosis (CF) patients with identical CF transmembrane regulator (CFTR) genotype, suggesting genetic modifiers exist. One potential modifier is the Toll-like receptor 4 (TLR4) gene. TLR4 binds lipopolysaccharide (LPS), a constituent of Pseudomonas aeruginosa (PA), activating innate immunity and promoting inflammation. TLR4 polymorphisms are associated with LPS-hyporesponsiveness and may be protective in CF due to decreased inflammation. Materials and Methods: DNA was extracted from blood of recruited CF subjects, and PCR performed to establish TLR4 D299G genotype. Case-notes were reviewed to obtain clinical data. Subjects possessing the TLR4 299G allele were compared with age, sex, and CFTR genotype-matched wild-type (299DD) subjects and also with all controls. Results: 100 subjects (mean age 8.9 years) were studied, with 11 299DG heterozygotes identified. On case-matched analyses, no statistically significant differences between groups were found for mean?SEM rates of change of %predicted FEV1/year (0.9?2.3 (DD) vs. ?3.9?2.8 (DG), p=0.22), %predicted FEV1 (76?8 vs. 74?11), p=0.91), or z scores for height (?0.47?0.26 vs. ?0.24?0.19, p=0.48) and weight (?0.01?0.22 vs. ?0.29?0.27, p=0.44). Median?SE survival age at first PA isolation was also not significantly different (3.5?2.1 vs. 6.5?2.4 years, p=0.29). No statistically significant differences were noted when 299DG heterozygotes were compared with all controls. Conclusions: Potential reasons for absence of modifier effect include the basolateral location of TLR4 receptors on respiratory epithelium, or because inflammatory response to PA in the CF airway is so overwhelming that even a blunted response (as suggested for the 299G allele) results in increased inflammation and lung damage.

Ornithine transcarbamylase gene mutations and genotype-phenotype correlation in Polish patients with hyperammonemia type 2

80%

Popowska E., Ciara E., Rokicki D., Pronicka E.

1999

vol. 40

issue 1

43-52

Ornithine (OTC) deficiency is an X-linked disorder of the urea cycle inherited by a partially dominant trait. We studied one boy with a positive family history of sudden infant death syndrome (SIDS) and four girls with suspected OTC deficiency basing on pedigree analysis, spontaneous episodes of hyperammonemia and orotic aciduria, and on results of the allopurinol loading test. Four different point mutations, N198K in exon 6, A209V and E326K in exon 9, and IVS nt-2 aRg in splice acceptor site in intron 7 were identified in the OTC gene. In addition, one common polymorphism in exon 8 (Q270R) with normal OTC activity was observed. All the mutations were detected in heterozygous girls and, except one, in the patients' asymptomatic mothers. In the latter single case the mutation had occurred de novo. All of the affected patients developed a positive allopurinol test. Four affected but asymptomatic women (mothers and a sister of the patients) revealed normal or only slightly increased orotic aciduria following allopurinol ingestion. Our observation supports the probability of undefined or false negative allopurinol test results reported previously for heterozygous females.

Single nucleotide polymorphisms in the RET gene and their correlations with Hirschsprung disease phenotype

80%

Smigiel R., Lebioda A., Patkowski D., Czernik J., Dobosz T., Pesz K., Kaczmarz M., Sasiadek M. M.

issue 3

261-267

Hirschsprung disease (HSCR) is a congenital, heterogeneous disorder, characterized by the absence of intestinal ganglion cells. Recent advances show that the RET gene is a major locus involved in the pathogenesis of HSCR. The aim of this study was to analyse if the HSCR phenotype in the Polish population is associated with the presence of polymorphisms in exons 2, 3, 7, 11, 13, 14 and 15 of the RET gene. Molecular results were compared with clinical and long-term follow-up data in 70 Polish patients with HSCR (84.3% with a short segment and 15.7% with a long segment of aganglionic gut). Single-nucleotide polymorphisms were analysed by using the minisequencing SNaPshot multiplex method. The 135G>A polymorphism in RET exon 2 was overrepresented in HSCR patients, compared with a healthy control group. Moreover, the 135G>A variant was shown to be associated with the severe HSCR phenotype. Two other polymorphisms, 2071G>A in exon 11 and 2712C>G in exon 15, were underrepresented in the patients. The results confirm that these RET polymorphisms play a role in the aetiology of HSCR.

Refine search results

2 Journal of Applied Genetics

1 Archivum Immunologiae et Therapiae Experimentalis

2 2006

1 1999

1 Allen J.

1 Ciara E.

1 Czernik J.

1 Dobosz T.

1 Elrayess M.

1 Fidler K.

1 Jaffe A.

1 Kaczmarz M.

1 Klein N.

1 Lebioda A.

1 Patkowski D.

1 Pesz K.

1 Popowska E.

1 Pronicka E.

1 Rokicki D.

1 Sasiadek M. M.

1 Smigiel R.

1 Urquhart D. S.

Search results

Modifier effect of the Toll-like receptor 4 D299G polymorphism in children with cystic fibrosis

Ornithine transcarbamylase gene mutations and genotype-phenotype correlation in Polish patients with hyperammonemia type 2

Single nucleotide polymorphisms in the RET gene and their correlations with Hirschsprung disease phenotype