Sinan Süzen

Are PON1 Q/R 192 and M/L 55 polymorphisms risk factors for diabetes complications in Turkish population?

OBJECTIVES We investigated whether the human serum paraoxonase (PON1) Q/R 192 and M/L 55 polymorphisms are associated with the complications of the type 2 diabetes (T2D). DESIGN AND METHODS Study group was consisted of 50 healthy subjects and 100 type 2 diabetes mellitus (DM) patients. Following measuring of serum PON1 activity, isolation of DNA and genotyping analyses were performed. RESULTS PON1 activity of the patients with complications was significantly reduced by 23.5% compared to the group of diabetic patients and by 26.3% than the controls. According to multivariate analysis, we observed a three times significant effect of Q/R 192 polymorphism on the susceptibility to the occurrence of complications. CONCLUSIONS Protective effects of paraoxonase against peroxidation of LDL particles are important in T2D complications. Although both of the two polymorphisms are associated, 192 polymorphism seems to be stronger predictor of the risk of diabetic complications.

The relationship of PON1 QR 192 and LM 55 polymorphisms with serum paraoxonase activities of Turkish diabetic patients.

Paraoxonase (PON1) is a serum esterase responsible for the protection against xenobiotics toxicity such as paraoxon. Alterations in PON1 concentrations have been reported in a variety of diseases including diabetes mellitus (DM). It has been shown that the serum PON1 concentration and activity are decreased in patients with both type 1 and type 2 DM. This study aimed to investigate the lipid profiles and the relationship between PON1 activity and PON1, QR192 and LM55 polymorphisms in Turkish type 2 diabetic patients and non-diabetic control subjects. According to our results, RR variant had significantly higher PON activity than QQ and QR variants (p < 0.01) and LL variant had significantly higher PON activity than MM variant in both control and patient groups (p < 0.05). In conclusion, we found that PON1 192RR and 55LL genotypes are associated with higher PON activity than QQ and MM genotypes. This may be more protective to lipid peroxidation.

DNA integrity in patients undergoing hyperbaric oxygen (HBO) therapy.

Hyperbaric oxygen (HBO) therapy is successfully applied for a wide variety of diseases. However, recent studies in humans undergoing (HBO) therapy have revealed that HBO is able to induce oxidative DNA damage especially in lymphocytes while the biological significance of this outcome is still not clear. HBO mediated DNA damage in lymphocytes has been determined by using the alkaline version of the comet assay in order to detect DNA strand breakages in patients undergoing HBO therapy. Blood samples were obtained from 100 voluntary patients and were drawn by venipuncture before and immediately after the first session of HBO treatment. The DNA damaging effect of HBO has also been evaluated in the fifth session of HBO therapy. DNA strand breakages were significantly increased after the first session of HBO treatment. However the elevated DNA strand breaks returned to their normal levels in lymphocytes after two hours of in vitro incubation. The elevated DNA strand breaks consistently decreased and reached to the baseline levels after the fifth session of HBO therapy. The results of this study, conducted in patients undergoing HBO therapy, support the existence of the previously reported cellular adaptive response against HBO mediated oxidative DNA damage in experimental studies.

Cytochrome P450 (CYP) and glutathione S-transferases (GST) polymorphisms (CYP1A1, CYP1B1, GSTM1, GSTP1 and GSTT1) and urinary levels of 1-hydroxypyrene in Turkish coke oven workers

Genetic polymorphisms of xenobiotic metabolizing enzymes have been associated with cancer risk. We evaluated the influences of genetic polymorphisms of polycyclic aromatic hydrocarbon (PAH) metabolizing enzymes on urinary 1-hydroxypyrene (1-OHP) excretion in Turkish coke oven workers. Urinary 1-OHP was analyzed by HPLC after enzymatic hydrolysis. Lymphocyte DNA was used for PCR-based genotyping of cytochrome P450 (CYP) polymorphisms (CYP1A1 and CYP1B1) and glutathione S-transferases (GST) polymorphisms (GSTM1, GSTT1 and GSTP1). The mean urinary 1-OHP levels of coke oven workers were significantly higher than that of controls. No significant difference was detected in the mean urinary 1-OHP levels of smokers and non-smokers either for coke oven workers or controls. Genetic polymorphisms of the CYPs and GSTs studied had no significant influence on 1-OHP excretion in coke oven workers, but in the control group the urinary 1-OHP levels of individuals carrying the GSTT1- genotype were significantly higher than those of individuals carrying GSTT1+ genotype. The duration of occupational exposure and metabolic genotype for GSTT1 were the significant predictors of urinary 1-OHP levels. The control individuals carrying combined GSTM1-/GSTT1- genotypes also had significantly higher levels of urinary 1-OHP than those of individuals carrying GSTM1+/GSTTI+, GSTM1-/GSTT1+, and GSTM1+/GSTT1- genotypes. These results indicate that urinary 1-OHP is a sensitive indicator of recent human exposure to PAHs and that genetic polymorphism of GSTT1 may also to some extent reflect the interindividual variation in susceptibility to PAHs only at low PAH exposure.

Evaluation of the biological threshold value of urinary cadmium concentration in a group of workers

The most typical feature of chronic cadmium intoxication is kidney damage. Cadmium af fec ts reabsorption functions of the proximal tubuli and the first sign of which is usually an increase in urinary excretion of low molecular weight proteins (e.g., 62-microglobulin, retinol-binding protein, al-microglobulin), known as microproteinuria (Friberg et al. 1986; Lauwerys and Bernard 1986; Thun and Clarkson 1986). 62-microglobulin, a major component of the low molecular weight proteins in the urine of cadmium workers, increases with renal tubular damage. Microproteinuria can be defined as 62-microglobulin in urine>300 ug/g creatinine (Roels et al. 1991). Some researchers have shown that the concentration of cadmium in urine (which reflects the renal burden of cadmium) above which the risk of occurence of microproteinuria significantly increases, is around 10 lag/g creatinine (Bernard et al. 1979; Buchet et al. 1980; Lauwerys et al. 1979). It has been also shown that cadmium induced microproteinuria is irreversible(Elinder et al. 1985; Roels et al. 1989).

A Genotyping and Phenotyping Study Concerning the Possible Effects of Some Inflammatory Cytokine Gene Polymorphisms on the Development of Coal Workers’ Pneumoconiosis

Cytokines are important for playing a major role in several inflammatory reactions resulting in development of several diseases as well as Coal Worker’s Pneumoconiosis (CWP). Coal dust exposure stimulates inflammatory response leading to enhanced cytokine release from monocytes such as TNF-alpha and IL1. These released cytokines are the key points in the pathogenesis of CWP. The present study aimed to seek the cytokine gene profiles of Turkish coal workers by genotyping and phenotyping analysis of important CWP-related proinflammatory cytokines; TNF-alpha, IL1-alpha and IL1-beta. According to the genotyping results, TNFA –238 gene polymorphism was appeared to be a risk factor in development of CWP (OR=3.79) and regarding to the phenotyping analysis, both TNF-alpha and IL1 cytokine releases from the monocytes in CWP patients were enhanced significantly compared to the healthy workers. Therewithal, LPS and coal dust stimulated TNF-alpha release were higher significantly in allele 2 carriers than allele 1 carriers in both of the groups. These data propose that coal dust-induced TNF-alpha release from monocytes may be a valuable biomarker of CWP.

Antioksidan gen polimorfizmlerinin baş ve boyun kanserinde araştırılması

Yassi hucreli bas ve boyun kanseri (YHBBK) ciddi bir saglik problemidir ve dunyada en sik gorulen kanser turlerinden biridir. Bu kanser turunun etiyolojisinde ana faktor olarak tutun kullanimi yer almaktadir. Duman karsinojenleri ve serbest radikaller DNA, RNA, lipitler ve proteinler gibi biyomolekullere zarar verebilir. Karsinojenik bilesiklere maruziyetin etkilerine ilave olarak, kanser gelisimi, bireylerin kanser yatkinligina bagli olabilir.Bu calismanin birincil amaci katalaz (KAT, -262C/T), mangan-superoksit dismutaz (SOD2, Val16Ala), ve glutatiyon peroksidaz-1 (GPX1, Pro198Leu) genlerindeki kalitsal farkliliklari olan bireylerin bas boyun kanser riskinin arttigi hipotezini test etmektir.Bu calismada KAT -262 C/T degisimi 205 saglikli bireyle 113 YHBB kanserli hasta arasinda polimeraz zincir reaksiyonu (PZR) ve restriksiyon parca uzunluk polimorfizmi (RPUP) yontemi kullanilarak analiz edilmistir. GPX1 ve SOD2 polimorfizm analizleri ayni teknikler kullanilarak 139 YHBB kanser hastasi ve 265 saglikli bireyde yurutulmustur.Calismamiz sonucunda katalaz geninin arastirilan polimorfizmde sirasiyla CC, CT ve TT genotipine ait 138 (% 67,32), 54 (% 26,34), 13 (% 6,34) kontrol grubunda, CC genotipine ait 64 (% 56,6), CT genotipine ait 44 (% 39), TT genotipine ait 5 (% 4,4) hasta ornegi sonucu elde edilmistir. BBK kanserinde arastirilan polimorfizmin hastalik gelisme risk orani CT genotipi icin OR: 1,75 [%95 CI 1.06- 2,88] ve TT genotipi icin OR: 0,82 [%95 CI 0,28-2,42] ‘dir. Calismanin sonucunda katalaz -262 C/T degisimi BBK gelisiminde oenmli bir rolunun olmayabilecegi gozlenmistir. Genler teker teker incelendiklerinde tum numuneleri iceren genel grupta, erkekler grubunda ve sigarayi halen icen ve birakmis kisilerin bulundugu sigara icenler grubunda SOD2 heterozigot genotiplerini tasiyan kisiler kontrol grubuna gore riskli bulunmustur. OR degerleri bu gruplar icin sirasiyla verilmistir OR: 1,902; %95 CI 1,100-3,284, OR:2,062; %95 CI 1,116-3,811, OR:2,126; %95 CI 1,130-3,997. GPX1 Leu/Leu allelini tasiyan kisiler, erkekler grubunda ve sigara icenler grubunda YHBB kanseri icin riskli bulunmustur. OR degerleri sirasiyla verilmistir OR: 2,148; %95 CI 1,001-4,611, OR: 2,380; %95 CI 1,079-5,249. Sonuclarimiza gore GPX1 Leu/Leu ve SOD2 Val/Ala genotiplerini tasiyan kisilerde kanser risk artisi gozlenmistir.Potansiyel olarak genotoksik bilesiklerin detoksifikasyonunda onemli rol oynayan KAT, GPX1 ve SOD2 enzimlerinin savunma sisteminde onemli rolleri vardir. Bu genlerdeki polimorfizmlerin arastirilmasi kanser gelisiminde rol oynayan genetik faktorlerin anlasilmasina katki saglamaktadir.