A bstractEssential hypertension is a m ultifactorial disease in w hich genetic and envirom ental factors play an im portant role. These factors differ in each population. As there are no existing data for the Turkish population, w e investigated four Renin Angiotensin System (RAS) gene polym orphism s, the angiotensin converting enzym e (ACE), angiotensinogen (AG N) M 235T/T174M and angiotensin II type 1 receptor A1166C polym orphism in 109 hypertensive and 86 norm otensive Turkish subjects. Polym erase Chain Reaction (PCR) and Restriction Fragm ent Length Polym orphism (RFLP), and agarose gel electrophoresis tecniques w ere used to determ ine these polym orphism . The frequencies of person that carry ACE D allel (DD+ID) w as significantly higher in hypertensive group (99.1% ) than controls (80%) (P 0.000). M235T TT genotype was also found significantly higher in hypertensives than control group (20% vs 2.7% ; P 0.001). The frequency of AG N 174M allele w as higher in the hypertensive group than control subjects (8.76% vs 4.81% ). Frequency of ATR1 C allele (AC+CC genotypes) w as found higher hypertensives than controls (39.4% vs 25.9% ; P = 0.054). O ur results suggest that an interaction exists between the RAS genes and hypertension in Turkish population.

Release of noradrenaline (NA) from isolated rat iris during perfusion in K+-free medium was confirmed. Direct The phenomenon of neurotransmitter release in quanta by the process of exocytosis is well accepted [Smith and Winkler, 1972] together with evidence that depolarization produces an increase in Nat and Cat + permeability in the neuronal basal membrane [Katz and Miledi, 1967, 1970]. Studies by Paton, Vizi and Zar [1971] and Vizi [1977] have led to the suggestion in a detailed review by Vizi [1978] that passage of the action potential across the nerve terminal with the accompanying depolarization and influx of Nat ions followed by Ca+ + ions, results in an inhibition of Na+/K+ ATPase activity at the inner side of the presynaptic membrane, producing permeability change in the membrane with transmitter release. He further suggested that release is terminated by stimulation of the membrane ATPase and that a sodium pump inhibition-stimulation cycle enables transmitter release to be quantized.A great deal of experimental evidence was assessed by Vizi [1978] to support this hypothesis. However, there are points requiring clarification. Vizi [1978] himself stressed the important unresolved question of how membrane ATPase inhibition by Ca"+ is terminated. In addition, it is difficult to see how one can reconcile the relatively long turnover time of the sodium pump with the much shorter time involved in transmitter release in response to stimulation.To quote Vizi [1978], most of the supportive evidence for his hypothesis comes from experiments in which application of drugs or conditions known to inhibit or stimulate membrane ATPase activity produce changes in rate of transmitter release, e.g. Nat or Kt deprivation, or ouabain [Paton et al., 1971;

We investigated the effect of PON 55 and PON 192 polymorphisms on serum PON1 activity and lipid profiles in 213 non-insulin dependent diabetes mellitus (NIDDM) individuals and 116 non-diabetic controls among Turkish subjects. The distribution of PON 55/192 gene polymorphism was determined by polymerase chain reaction-based restriction fragment length polymorphism. Serum lipid levels were measured enzymically. PON activity was measured by spectrophotometric assay of p-nitrophenol production following addition of paraoxon. We found that PON 55 and 192 genotype distribution was similar in patients and controls and paraoxonase activity was generally lower in diabetics than in control subjects. We showed that PON 55 and 192 genotypes have a major effect on serum PON activity. PON 192 BB homozygotes had significantly higher PON activity than AA and AB genotypes among the control and NIDDM populations (p<0.001). PON 55 MM homozygotes had significantly lower PON activity than did LL and LM genotypes in control and NIDDM populations (p<0.05). The PON1 55 and 192 polymorphisms did not consistently influence the serum lipid profiles in either population. In conclusion, our results suggest that the paraoxonase activities are affected by PON1 genetic variability in Turkish NIDDM patients and controls.

The effects of 1,25-dihydroxyvitamin D3 are mediated by binding to a specific intracellular vitamin D receptor (VDR), which has been identified in a variety of tissues. Certain polymorphisms in the VDR gene have been associated with various neoplasms. For this purpose, we studied whether VDR TaqI or FokI genotype are associated with serum 25-hydroxyvitamin D3 in 52 controls and 26 patients with colorectal cancer. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), and agarose gel electrophoresis tecniques were used to detect these polymorphisms. We measured 25-hydroxyvitamin D3 serum levels by ELISA. The frequencies of the FF, Ff and ff genotypes were 73.1%, 11.5%, 15.4% in colorectal cancer patients and 38.5%, 59.6%, 1.9% in healthy controls, respectively. We observed the T allele in 50% and 58.7%, and the t allele in 50% and 41.3% of colorectal cancer patients and the control group, respectively. In patients with colorectal cancer who have TT genotype, serum 25-hydroxyvitamin D3 level was lower than those with Tt/tt genotype (p:0.016). The frequency of subjects with TTFf or TtFf genotype in colorectal cancer patients was very low compared with all other genotypes (OR = 0.112; 95%CI 0.030-0.419). These data suggest that VDR TtFf or TTFf genotypes may protect against colorectal carcinogenesis. However, further studies are necessary to confirm these findings.

Methylenetetrahydrofolate reductase (MTHFR) is an enzyme (EC 1.5.1.20), that reduces 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a carbon donor for the homocysteine to methionine conversion. MTHFR is a key enzyme that regulates folate metabolism which has an important role in DNA synthesis, DNA repair and methylation. The association between MTHFR C677T polymorphism and breast cancer has been investigated in several previous studies. Some researchers have shown an association between C677T polymorphism and breast cancer, but not all researchers found this association however. This study was designed to investigate, in the Turkish population, the association of MTHFR C677T polymorphism and breast cancer. Forty women patients with breast cancer and 68 healthy women were included in the study. MTHFR gene polymorphism was determined by the PCR-RFLP method. SPSS 10.0 for windows was used to determine statistical significance. No differences were observed in the distribution of MTHFR genotypes or allele frequencies in the cases versus the controls. It was found that the frequencies of MTHFR polymorphism were 55%, 40%, 5% for CC, CT, TT genotype in patients and 56%, 38%, 6% in healthy controls respectively. Furthermore, association was observed among family history, metastatic risk and MTHFR genotypes in patients. Our data fail to support a relationship between MTHFR C677T and the risk for breast cancer. It may be that there are ethnic differences in terms of this relationship.