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Copyright of Canadian Journal of Physiology & Pharmacology is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Context: Presbycusis, an age-related hearing impairment (ARHI), represents the most common sensory disability in adults. Today, the molecular mechanisms underlying presbycusis remain unclear. This is in particular due to the fact that ARHI is a multifactorial complex disorder resulting from several genomic factors interacting with lifelong cumulative effects of: disease, diet, and environment. Objective: Identification of novel biomarkers for presbycusis. Materials and methods: We selectively ascertained 18 elderly unrelated women lacking environmental and metabolic risk factors. Subsequently, we screened for methylation map changes in blood samples of women with presbycusis as compared to controls, using reduced representation bisulfite sequencing. We focused on hypermethylated cytosine bases located in gene promoters and the first two exons. To elucidate the related gene expression changes, we performed transcriptomic study using gene expression microarray. Results: Twenty-seven genes, known to be expressed in adult human cochlea, were found in the blood cells to be differentially hypermethylated with significant (p < 0.01) methylation differences (>30%) and down-expressed with fold change >1.2 (FDR <0.05). Functional annotation and qRT-PCR further identified P2RX2, KCNQ5, ERBB3 and SOCS3 to be associated with the progression of ARHI. Discussion and conclusion: Down-expressed genes associated with DNA hypermethylation could be used as biomarkers for understanding complex pathogenic mechanisms underlying presbycusis. [ABSTRACT FROM AUTHOR]

Retraction: ‘Genotyping of Tunisian azoospermic men with Sertoli cell‐only and maturation arrest‘ by Hadjkacem‐Loukil, L., Hadj‐kacem, H., Hadj Salem, I., Bahloul, A., Fakhfakh, F. and Ayadi, H. The above article, published online on 6 July 2011 in Wiley Online Library ( www.onlinelibrary.wiley.com), has been retracted by agreement between the journal Editor‐in‐Chief, Ralf Henkel, and Blackwell Verlag GmbH. The retraction has been agreed due to unverifiable data and authorship issues. Reference Hadjkacem‐Loukil, L., Hadj‐kacem, H., Hadj Salem, I., Bahloul, A., Fakhfakh, F. and Ayadi, H. (2011), Genotyping of Tunisian azoospermic men with Sertoli cell‐only and maturation arrest. Andrologia. doi: 10.1111/j.1439‐0272.2010.01088.x [ABSTRACT FROM AUTHOR]

FOXE1 polyalanine tract (poly-Ala) has been associated with thyroid dysgenesis. Recently, the SNP (rs1867277:-238G>A) within the FOXE1 5'UTR was involved in the genetic susceptibility to thyroid cancer (TC). In the aim to assess the influence of FOXE1 poly-Ala length on the genetic susceptibility to TC and autoimmune thyroid diseases (AITD), a case-control design (including 261 Tunisian AITD, 170 Spanish TC and respectively 171 and 218 matched healthy subjects) was performed. The effect of Ala length and rs1867277 alleles on FOXE1 expression was investigated by mRNA relative real time quantification on 8 papillary thyroid carcinoma (PTC) and 10 Graves' disease (GD) genotyped thyroid biopsies. The fluorescent genotyping of poly-Ala polymorphism revealed nine alleles (from 12 to 22 repetitions). The association of poly-Ala polymorphism with AITD was rejected (Pc>0.05). However, a significant association was found with TC. In addition, the genotypic distributions revealed the predispositional effect of the 16/16 genotype (OR = 2.71; 95%CI: 1.36-5.42; p=0.001) and the protector effect of the 14/14 genotype (OR= 0.46; 95%CI: 0.29-0.72; p=0.003). The quantification studies reveal that FOXE1 transcripts were less abundant in PTC than GD samples. Moreover, FOXEI gene was 4,8 fold less expressed among PTC protected patients compared to homozygous 16/16-A/A. In conclusion, by exploring the poly-Ala polymorphism, we confirmed the involvement of {\it FOXE1} gene in the genetic susceptibility to TC and we reported its down expression among PTC tissues. [ABSTRACT FROM AUTHOR]

Angle-closure glaucoma (ACG) is a subset of glaucoma affecting 16 million people. Although 4 million people are bilaterally blind from ACG, the causative molecular mechanisms of ACG remain to be defined. High intraocular pressure induces glaucoma in ACG. High intraocular pressure traditionally was suggested to result from the iris blocking or closing the angle of the eye, thereby limiting aqueous humor drainage. Eyes from individuals with ACG often have a modestly decreased axial length, shallow anterior chamber and relatively large lens, features that predispose to angle closure. Here we show that genetic alteration of a previously unidentified serine protease (PRSS56) alters axial length and causes a mouse phenotype resembling ACG. Mutations affecting this protease also cause a severe decrease of axial length in individuals with posterior microphthalmia. Together, these data suggest that alterations of this serine protease may contribute to a spectrum of human ocular conditions including reduced ocular size and ACG. [ABSTRACT FROM AUTHOR]

In this study, a sample of 126 Kuwaiti was analysed using 12 Y-chromosome short tandem repeat (STR) polymorphisms. A total of 101 different haplotypes were identified, among which 87 were individual specific. The high haplotype diversity (0.994) supports the usefulness of Y-STR markers in Kuwaiti population diversity investigation. Our results suggest a close genetic relationship between Kuwait and other populations of the Arabian Peninsula, and an even more pronounced similarity of Kuwaiti populations and Yemenis and Saudi Arabians. [ABSTRACT FROM AUTHOR]

Deleterious mutations of SLC26A4 cause Pendred syndrome (PS), an autosomal recessive disorder comprising goitre and deafness with enlarged vestibular aqueducts (EVA), and nonsyndromic hearing loss (NSHL). However, the SLC26A4 hyperactivity was recently associated with the emergence of autoimmune thyroid diseases (AITD) and asthma among human and mouse model. Here, by direct sequencing, we investigate the sequences of the 20 coding exons (2 to 21) of SLC26A4 and their flanking intron-exon junctions among patients affected with Graves' disease (GD) hyperthyroidism. Ten mono-allelic variants were identified, seven of which are intronic and previously unreported. Two, c.898A>C (p.I300L) and c.1061T>C (p.F354S), of the three exonic variants are non synonymous. The p.F354S variant is already described to be involved in PS or NSHL inheritances. The exploration by PCR-RFLP of p.I300L and p.F354S variants among 132 GD patients, 105 Hashimoto thyroiditis (HT), 206 Healthy subjects and 102 families with NSHL have shown the presence of both variants. The p.F354S variation was identified both among patients (1~HT and 3 GD) and healthy subjects (n=5). Whereas, the p.I300L variant was identified only in GD patients (n=3). Our studies provide evidence of the importance of systematic analysis of SLC26A4 gene sequences on models other than deafness. This approach allows the identification of new variants and the review of the pathogenic effects of certain mono-allelic variants reported responsible for PS and NSHL development. [ABSTRACT FROM AUTHOR]

Background: Protein tyrosine phosphatase (PTPN22) is involved in the negative regulation of T-cell responsiveness. The association of a coding variant of the PTPN22 gene (R620W) with a number of autoimmune diseases has been described. Aim: The present study investigated whether PTPN22 gene polymorphism was also involved in the genetic predisposition to autoimmune thyroid diseases (AITDs) and rheumatoid arthritis (RA) in a Tunisian case control study. Subjects and methods: DNA samples from 150 patients affected with RA, 204 patients affected with AITDs and 236 healthy controls were genotyped for PTPN22 R620W polymorphism (1858C/T). Genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism method. Results: No significant differences in T allele frequency (2.3% in RA patients and 1% in AITDs patients vs 2.6% in controls; p=0.85 and p=0.08, respectively) and in genotype frequencies were detected between RA patients and controls (p=0.15) and between AITDs patients (p=0.11). Stratifying patients affected with AITDs according to their phenotype (Graves' disease and Hashimoto's thyroiditis) and RA patients according to the presence of rheumatoid factor (RF) and antibodies against cyclic citrullinated peptides (ACPA) did not show any significant association with PTPN22 R620W allele (p>0.05). Conclusion: Our data suggest that the PTPN22 C1858T single nucleotide polymorphism has no or minor effect on RA and AITDs susceptibility in the Tunisian population. [ABSTRACT FROM AUTHOR]