Gazi University, Faculty of Medicine.

Hypoxia-inducible factor-1 (HIF-1), an important genetic component of angiogenesis, becomes stable as a response to tumor hypoxia and facilitates tumor survival. The polymorphisms of the HIF-1alpha gene may cause changes in the activity of the protein which serves as a transcription factor for many genes in tumorigenesis. In this study, we have investigated the relationship between seven HIF-1alpha polymorphisms [C>T substitution in intron 8 (rs10873142), T418I (rs41508050) in exon 10, P564P (rs41492849), L580L (rs34005929), P582S (rs11549465), A588T (rs11549467) in exon 12 and dinucleotide GT repeat in intron 13 (rs10645014)] among lung cancer patients in the Turkish population. Genomic DNA was isolated from 141 lung cancer cases and 156 controls and subjected to PCR for amplification. Genotyping was carried out with RFLP and DNA sequencing methods. There was no significant difference between lung cancer cases and controls in terms of the distribution of genotyping frequencies of seven HIF-1alpha polymorphisms (P>0.05). No significant relationship was found between the C>T substitution in intron 8 and P582S haplotypes and development of lung cancer. Also, no significant difference was observed between the genotypes and clinopathological characteristics of the cases. These findings showed that polymorphisms of the HIF-1alpha gene did not confer susceptibility to lung cancer.

Department of Medical Biology, Faculty of Medicine, Suleyman Demirel University, 32260 Cunur, Isparta, Turkey, nilufersahin@yahoo.com.

Mutations in the ganglioside-induced differentiation-associated protein 1 gene (GDAP1) cause Charcot-Marie-Tooth type 2 (CMT2), a severe autosomal recessive form of neuropathy associated with axonal phenotypes. It has been screened in this study for the presence of mutations in the coding region of GDAP1, which maps to chromosome 8q21, in a family with CMT2. To date, 29 mutations in the GDAP1 have been reported in patients of different ethnic origins. Here, we report a novel missense mutation (c.836A>G), and two polymorphisms: a silent variant (c.102G>C), and a 5′-splice site mutation (IVS5+24C>T) in GDPA1 gene identified in a five generation Turkish family with autosomal recessive CMT2.

Molecular Medicine Laboratory, Department of Pediatrics, Faculty of Medicine, Ege University, Izmir, Turkey.

Angiotensin converting enzyme (ACE) plays an essential role in the renin-angiotensin system. It converts angiotensin I to angiotensin II and inactivates bradykinin and tachykinins. Numerous studies have been published investigating associations of the ACE gene I/D polymorphism with various pathophysiological conditions. We examined the prevalence of the ACE I/D polymorphism in a sample of healthy volunteers from western Turkey, including 1063 healthy Turkish controls. Analysis of the ACE I/D gene polymorphisms by polymerase chain reaction found frequencies of 16.1% for the II genotype, 47.7% for the ID genotype, and 36.2% for the DD genotype. The allele frequency was 39.9% for the I alleles and 60.1% for the D allele. This study demonstrates that the allele and genotype frequency values for the Turkish population are similar to previously published frequencies for Caucasian populations.

Gazi University, Faculty of Medicine.

Genetic and environmental factors are involved in Prostate Cancer (PCa) etiology. Single nucleotide polymorphisms (SNPs) may contribute to the PCa pathogenesis. The goal of this study is to determine the role of vitamin D receptor (VDR) gene polymorphisms and haplotypes in the development and progression of sporadic PCa. One hundred and thirty-three PCa patients and one hundred and fifty-seven age-matched healthy controls were genotyped for the ApaI (rs7975232), BsmI (rs1544410) and TaqI (rs731236) polymorphisms in VDR gene by using polymerase chain reaction-restriction fragment length polymorphism. An association was observed between the ApaI polymorphism and PCa predisposition (P = 0.03). When compared with AA genotype, there was a highly notable difference in the frequencies of the Aa (P = 0.02), aa (P = 0.026) and ApaI “a” allele carriers (Aa+aa) (P = 0.009) genotypes. Furthermore, we found a statistical difference in the allele frequencies of the ApaI polymorphism between the sporadic PCa patients and control subjects (P = 0.013). The genotype distribution for the BsmI and TaqI polymorphisms were similar between cases and controls (P >0.05). No clinically significant relationship was found between the three-locus haplotypes and development of sporadic PCa. The genotype frequencies for the three polymorphisms of the VDR gene within subgroups of PCa (defined by tumor stage, Gleason score, PSA levels) were also analyzed, but no statistically noteworthy difference was observed (P >0.05). As far as we know, this is the first study which investigates the relationship between VDR genotypes and sporadic PCa in the Turkish Population. Our findings suggest that the VDR ApaI (rs7975232) polymorphism may play a role in the development of sporadic PCa.

Division of Medical Genetics and Biochemistry, Faculty of Medical Sciences, University of Fukui, Eiheiji-cho, Fukui, Japan.

Angiogenin and ribonuclease 2 (RNase 2) are members of the human RNase superfamily. Although three potential single nucleotide polymorphisms (SNPs) in these genes, which could give rise to an amino acid substitution in the protein, have been identified, relevant population data are not available, and accordingly they have not been applied to clinical-genetic analysis. For this purpose, a novel genotyping method for each SNP using the mismatched PCR-restriction fragment length polymorphism technique has been developed. Using this method, the genotype distribution of each SNP was investigated in six populations: Japanese (n = 167), Korean (n = 90), Mongolian (n = 92), Ovambos (n = 86), Turkish (n = 87), and German (n = 70). In all the populations, only one genotype was found in each SNP. Irrespective of differences in ethnic groups, the angiogenin and RNase 2 genes appear to exhibit markedly less genetic heterogeneity with regard to these SNPs. Copyright 2008 John Wiley & Sons, Ltd.