Investigation of the common paraoxonase 1 variants with paraoxonase activity on bone fragility in Turkish patients.

There is increasing evidence of a biochemical link between oxidative stress and bone metabolism. Oxidative stress has been shown to be involved in bone resorption as it causes loss of bone mineral density (BMD). Paraoxonase 1 (PON1), can prevent these effects of the oxidative stress on bone formation. It has been suggested that the PON1 gene as possibly implicated in reduced BMD in bone fragility cases. It has been hypothesized that PON1 gene polymorphisms may influence both the risk of osteoporosis and osteopenia occurrence and prognosis. The aim of our study is to evaluate the relationship between PON1 polymorphisms and bone fragility development. Seventy-four osteoporotic, 121 osteopenic and 79 nonosteoporotic postmenopausal women were recruited. For detection of the polymorphisms, polymerase chain reaction-restriction fragment length polymorphism techniques have been used. BMD was measured at the lumbar spine and hip by dual-energy X-ray absorptiometry. Distributions of PON1 (PON 192 and PON 55) polymorphisms in study groups were not significantly different. But, there was medium strength connection between in the osteopenic with control groups regarding PON1 55-PON1 192 haplotypes and we found a power strength connection between in the osteoporosis with control groups regarding PON1 55-PON1 192 haplotypes. Furthermore, subjects with PON1 192RR and PON1 55LL genotypes had lower PON activity values of osteoporotic subject compared to healthy control and this difference was statistically significant (p < 0.05). This result suggest that PON1 genotypes could be higher risk for osteoporosis, as determined by reduced BMD.

Vitamin D levels in children with recurrent tonsillitis.

AIM: Although recurrent tonsillitis can be the consequence of defects in immune system, the exact etiology of recurrent tonsillitis is not clear. In this study, our aim was to determine the serum vitamin D levels and vitamin D receptor polymorphism among children undergone tonsillectomy due to the recurrent tonsillitis. METHODS: A 106 children undergone tonsillectomy due to recurrent tonsillitis and a 127 healthy children aging between 2 and 12 years were enrolled in this study, to determine serum 25-hydroxyvitamin D level and vitamin D receptor gene polymorphisms (Apa1, Taq 1, fok1). Serum vitamin D level was measured with ELISA (nmol/L) and receptor gene polymorphism was determined by PCR. Vitamin D serum level below 80nmol/L was accepted as insufficient. RESULTS: The average serum vitamin D level was 176±79nmol/L in recurrent tonsillitis group and 193±56nmol/L in control group. There was no significant difference between the groups (p=0.13). In recurrent tonsillitis group, 18% (n=15) of children had their serum vitamin D levels below 80nmol/L. The vitamin D receptor gene polymorphism (APA1, TAQ 1, FOK 1) in each group was compared (AA, Aa, aa, TT, Tt, tt, FF, Ff, ff). There was no significant difference between the two groups. The vitamin D serum levels and receptor sub-genotypes are also compared, and there was no significant difference between the groups. CONCLUSION: There is no difference between the serum vitamin D level and receptor gene polymorphism among children with recurrent tonsillitis and healthy children. But vitamin D insufficiency is more prevalent in children with recurrent tonsillitis group (18%).

Cyclooxygenase-2 gene and lung carcinoma risk.

In this study, we aimed to investigate a possible association of the COX-2 polymorphisms with the risk of developing lung carcinoma. COX-2 (-765G→C; -1195A→G) gene polymorphisms were performed by polymerase chain reaction (PCR) and restriction fragment length polymorphism in 118 healthy individuals and 231 patients with lung carcinoma. The present study was the first that addressed the role of the COX-2-765G→C and -1195A→G polymorphisms in lung carcinoma in Turkish population. In the present study, we found that the frequencies of GG, CC, and CG genotypes of COX-2-765G→C and AA, GG, and AG genotypes of -1195A→G in our control group were 0.22, 0.22, 0.55 and 0.59, 0.0, 0.40, respectively. These frequencies in patient group were 0.34, 0.07, 0.58 and 0.74, 0.04, 0.24, respectively. There were statistically significant differences in COX-2-765G→C (P=0.0002) and -1195A→G genotypes (P=0.007) between the controls and patients. We found that individuals carrying -765 GG genotype and -765 G allele of COX-2 or 1195 AA genotype of COX-2 and -765G: -1195A haplotype had an increased risk for the development of lung carcinoma. In contrast, individuals with -765 CC, -1195 AG genotypes and -1195 G allele of COX-2 seem to be protective from lung carcinoma. We suggest that the COX-2-765G→C and -1195A→G genotypes may be a risk factor for lung carcinoma.

Paraoxonase 1 192 and 55 polymorphisms in osteosarcoma.

Paraoxonase is an HDL-associated enzyme that plays a preventive role against oxidative stres. Previous studies suggested that involved an amino acid substitution at position 192 gives rise to two alloenzymes with a low activity (Q allele) and a high activity (R allele) towards paraoxon. There also exists a second polymorphism of the human PON1 gene affecting amino acid 55, giving rise to a leucine (L-allele) substitution for methionine (M-allele). PON1 gene polymorphisms were studied in 50 patients with osteosarcoma and 50 healthy controls. Paraoxonase genotypes were determined by PCR-RFLP. We found a reduction in the frequency of PON1 192 R allele in patients (P=0.015). Besides, PON1 192 wild type QQ genotype (P=0.015) and PON1 55 wild type L allele (P=0.001) were higher in patients compared to healthy controls. PON1 192 QQ genotype was associated with osteosarcoma in multivariate logistic regression analysis. Our findings have suggested that PON1 192 wild type genotypes may be associated with a risk of developing osteosarcoma.

Association of monocyte chemotactic protein-1 and CC chemokine receptor 2 gene variants with preeclampsia.

Preeclampsia complicates 10% of pregnancies in developing countries. It is one of the leading causes of maternal and fetal/neonatal mortality and morbidity worldwide. It has been suggested that maladaptation of the maternal immune response during pregnancy might be a causal factor for preeclampsia. According to immune maladaptation hypothesis, preeclampsia is due to an inappropriate regulation of normally Th2-deviated maternal immune responses, leading to a shift toward harmful Th1 immunity. Several studies indicate that monocyte chemotactic protein-1 (MCP-1) and CC chemokine receptor 2 (CCR2) are involved in Th1 and Th2 immunity. In this study, we investigated the association between MCP-1 A-2518G and CCR2-V64I polymorphisms and preeclampsia. One hundred eighty preeclamptic pregnant women and 145 healthy controls were included in the study. We observed that in preeclamptic women, MCP-1 G: CCR2 Val haplotype was significantly higher when compared with other haplotypes. In conclusion, we stated that MCP-1 and CCR2 gene variants might be associated with preeclampsia.

Dual inhibition of wound healing and oxidative process by montelukast in experimental colon anastomoses.

BACKGROUND: The authors aimed to investigate the effects of montelukast (ML) on the experimental rat colon anastomosis. METHODS: A total of 80 Wistar albino rats were divided into 4 groups: sham-operated, colon anastomosis, and colon anastomosis with oral administration (OAML) and rectal administration of 10 mg/kg/d ML (RAML). Anastomotic bursting pressure, anastomotic hydroxyproline contents, malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPX), and superoxide dismutase (SOD) levels, and the expressions of Ki-67, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) with immunohistochemistry were assessed on postoperative day 5. RESULTS: Anastomotic bursting pressures and bFGF expressions were not changed, whereas tissue hydroxyproline concentrations and MDA levels and the expressions of Ki-67 and VEGF were significantly decreased, and GSH, GPX, and SOD levels were significantly increased in the OAML and RAML groups. CONCLUSION: ML causes impairment of wound healing without altering the anastomosis bursting pressure and reverses the oxidative damage of the colon anastomoses in rats.

Possible associations of APE1 polymorphism with susceptibility and HOGG1 polymorphism with prognosis in gastric cancer.

BACKGROUND: Multiple genetic and epigenetic alterations in several genes are implicated in the multistep process of human gastric carcinogenesis. In this study, we examined the polymorphisms of six DNA repair genes: APE1, HOGG1, XRCC1, XRCC3, XPD, and XPG in patients with gastric cancer (GC). PATIENTS AND METHODS: Forty patients with GC and 247 controls were included in this study. DNA polymorphisms were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) method. RESULTS: The frequency of the Asp/Glu genotype and Glu allele of APE1 in patients with GC was significantly higher than in the control group (p=0.05). We also observed a higher frequency of the Ser/Ser genotype of HOGG1 in grade III tumors, and in tumors with metastasis to adjacent tissue and solid organs (p<0.05). CONCLUSION: Our results suggest that (i) APE1 gene polymorphism may be associated with GC risk and (ii) HOGG1 gene polymorphism may be informative in the prognosis of GC.

Genetic variants of vascular endothelial growth factor and risk for the development of endometriosis.

BACKGROUND/AIMS: Endometriosis is regarded as a complex disese, in which genetic and environmental factors contribute to the disease phenotype. Whether vascular endothelial growth factor (VEGF) -460 C/T and +405 G/C polymorphisms are associated with susceptibility to endometriosis was investigated. PATIENTS AND METHODS: Diagnosis of endometriosis was made on the basis of laparoscopic findings. Stage of endometriosis was determined according to the Revised American Fertility Society classification. Sixty out of the 112 women enrolled had no endometriosis, 11 had mild or early-stage endometriosis and 41 had severe endometriosis. Polymerase chain reaction (PCR), restriction fragment length polymorphism and agarose gel electrophoresis techniques were used to determine the -460 C/T and +405 G/C genotypes. RESULTS: The VEGF +405 G/C genotype frequencies among the cases and controls were CC 55.8% and 35%; GC 30.8% and 50.0%; GG 13.5% and 15.0%, respectively. The allelic frequencies were C 71.15% (cases) and 60.0% (controls) and G 28.8% (cases) and 40% (controls). Patients with endometriosis had a higher incidence of the VEGF +405 CC genotype compared with the controls (p=0.027). Women with VEGF +405 CC genotype had 2.3-fold higher risk for endometriosis. VEGF +405 GC genotype and G allele in the control group was higher than the endometriosis group (p=0.039, p=0.027 respectively). The VEGF -460 C/T genotype frequencies among the cases were CC 21.2%, CT 26.9% and TT 51.9%; the C and T allelic frequencies were 34.6% and 65.3%, respectively. The VEGF -460 genotype frequencies among the controls were CC 31.70%, CT 18.3% and TT 50.0%; the C and T allelic frequencies were 40.8% and 59.1%, respectively (p>0.05). There was linkage disequilibrium between VEGF -460 C/T and +405 G/C polymorphisms (D': 0.197, r(2)=0.013). We observed that the VEGF 460T/405C haplotype frequency was significantly higher in patients compared to controls (p=0.011). CONCLUSION: Our data suggest that the CC genotype of VEGF +405 and 460T/405C haplotypes of VEGF may be associated with the risk of endometriosis, but the G allele of VEGF +405 appears to be protective against endometriosis.

Association of CCL2 and CCR2 gene variants with endometrial cancer in Turkish women.

Chemokines and their receptors play diverse roles in malignant tumor progression, particularly as key mediators of tumor stroma interactions. C-C motif chemokine ligand 2 (CCL2) also called monocyte chemoattractant protein-1 (MCP-1), belongs to the C-C motif chemokine sub-family and is currently believed to mediate its actions through one receptor, C-C motif chemokine receptor 2 (CCR2). CCL2 has been identified as a major chemokine inducing the recruitment of macrophages in human tumors, including those of the bladder, cervix, ovary, lung and breast. In this study of Turkish women, the association of CCL2 A2518G and CCR2 V64I polymorphisms with endometrial cancer was investigated using 50 endometrial cancer patients and 211 controls. In our study, individuals with CCL2 A2518G GG genotype showed a 6.7-fold increased risk for endometrial cancer (p<0.0001) and individuals with CCL2 A2518G A allele had a 7.14-fold lower risk of endometrium cancer (p<0.0001). Individuals carrying the CCR2 64I/64I genotype had a 4.13-fold increased risk for endometrial cancer (p<0.0001). We also found that individuals carrying the CCR2 wt allele had a 4.16-fold lower risk for endometrial cancer (p=0.005). We observed that the CCL2 G: CCR2 64I haplotype frequency was significantly higher in patients compared to controls (p=0.019). In conclusion, we state that there appears to be an association between polymorphism of CCL2 and its receptor CCR2 and endometrial cancer. To the best of our knowledge, this is the first study to show such an association.

Effect of genetic variants of chemokine receptors on the development of myocardial infarction in Turkish population.

Inflammation is a crucial component of coronary atherosclerosis and myocardial infarction (MI). Chemokine receptors are important modulators of inflammation. Polymorphisms in genes coding for chemokine receptors, CCR2 and CCR5, have been studied as genetic markers of coronary artery disease. In the present study, we investigated whether genetic variants of CCR2-V64I and CCR5-delta32 chemokine receptors have any effect on the development of myocardial infarction. A total of 146 MI patients and 202 control subjects were genotyped for CCR2 and CCR5. CCR2-V64I genotypes were not significantly different between patients with MI and controls (P > 0.05). CCR5-delta32 genotype distribution in cases was significantly different from that of controls (P = 0.042). The CCR5-delta32 wt/deletion genotype frequencies for controls and cases were 0.10 and 0.19, respectively and individuals with CCR5-delta32 wt/deletion genotype had a 2.13-fold increased risk of myocardial infarction (P = 0.0013). Individuals carrying the CCR5-delta32 heterozygote or homozygous variant genotype (deletion/deletion + wt/deletion) had a 1.96-fold increased risk of myocardial infarction compared with the wild-type genotype (wt/wt) (p: 0.016). In conclusion, our data have suggested that genetic variant of CCR5 might be associated with the development of MI. Further larger sample size studies are required to confirm our findings.

Association of interleukin 1beta gene (+3953) polymorphism and severity of endometriosis in Turkish women.

Endometriosis is regarded as a complex trait, in which genetic and environmental factors contribute to the disease phenotype. We investigated whether the interleukin (IL) 1beta (+3953) polymorphism is associated with the severity of endometriosis. Diagnosis of endometriosis was made on the basis of laparoscopic findings. Stage of endometriosis was determined according to the Revised American Fertility Society classification. 118 women were enrolled in the study. 78 women did not have endometriosis, 6 women had stage I, 3 had stage II, 13 had stage III and 18 had stage IV endometriosis. Polymerase Chain Reaction (PCR), Restriction Fragment Length Polymorphism (RFLP), and agarose gel electrophoresis techniques were used to determine the IL 1beta (+3953) genotype. Frequencies of the IL-1beta (+3953) genotypes in the control group were: CC, 0.397; TT, 0.115; CT, 0.487. Frequencies of the IL-1beta (+3953) genotypes in cases were: CC, 0.375; TT, 0.225; CT, 0.400. We found a 2.22 fold increase in TT genotype in the endometriosis group. However, the difference was not statistically significant (P > 0.05). We also observed an increase in the frequency of IL-1beta (+3953) T allele in the endometriosis group. However, the difference was not statistically significant. We also investigated the association between IL-1beta (+3953) polymorphism and the severity of endometriosis. The frequencies of CC+CT genotypes in stage I, III and IV endometriosis patients were 83.3, 84/6 and 72.2%, respectively; and TT genotypes were 16.7, 15.4 and 27.8%, respectively. We observed a statistically insignificant increase in TT genotype in stage IV endometriosis (P > 0.05). We suggest that IL-1beta (+3953) polymorphism is not associated with endometriosis in Turkish women.

Effect of paraoxonase 1 gene polymorphisms on clinical course of Henoch-Schönlein purpura.

BACKGROUND: Henoch-Schönlein purpura (HSP) is a systemic vasculitis; its pathogenesis is still unknown. Oxidative stress may play a role in the pathogenesis of HSP. Paraoxonase1 (PON1) is an antioxidant enzyme. Two polymorphisms have been defined in the coding region of the PON1 gene, Q/R192 and L/M55. In the present study, we aimed to investigate the effect of PON1 gene polymorphisms on the course and renal involvement of HSP in Turkish children. METHOD: Forty-six patients with HSP were compared with 34 healthy children regarding the distribution of PON1 polymorphisms. RESULTS: PON1 Q/R192 genotype distribution was 58.6% QQ, 32.6% QR and 8.8% RR in the HSP group and 14.3% QQ, 50% QR and 35.7% RR in the control group. The frequency of QQ genotype was higher in the HSP group, and the presence of QQ genotype increased the risk by 3.42-fold for developing HSP (p=0.000, Fisher exact test; odds ratio [OR] = 2.048; 95% confidence interval [95% CI], 1.396-3.00). PON1 L/M55 genotype distribution was 50% LL, 43.5% LM and 6.5% MM in the HSP group and 48% LL, 26% LM and 26% MM in the control group. The frequency of MM genotype was lower in the HSP group, and the presence of MM genotype decreased the risk by 7.38-fold for developing HSP (p=0.009, Fisher exact test; OR=7.380, 95% CI, 1.474-36.953). CONCLUSION: PON1 polymorphisms may contribute to the pathogenesis and course of HSP, but we suggest that further investigations with larger patient groups are required to confirm our results.

Apurinic/apyrimidinic endonuclease (APE1) gene polymorphisms and lung cancer risk in relation to tobacco smoking.

BACKGROUND: Polymorphisms altering DNA repair capacity may lead to synergistic effects with tobacco carcinogen-induced lung cancer risk. Based on this hypothesis, the relationship between APE1 polymorphism, smoking and the risk of lung cancer was explored. MATERIALS AND METHODS: The distribution of the APE1 Asp148Glu polymorphisms in 98 lung cancer patients and 67 healthy individuals were compared using PCR-RFLP analysis. RESULTS: Individuals carrying the APE1 Asp148Glu heterozygous and homozygous variant genotype had a 3.23-fold increased risk of lung cancer compared with these carrying the wild-type (Asp/Asp) genotype (p<0.0001), and those carrying the 148Glu homozygous genotype had a 3.17-fold increased risk (p=0.023). When stratified by smoking status, carriers of the Glu allele of APE1 were at a statistically increased risk of lung cancer among smokers (p=0.001). CONCLUSION: A statistically significant interaction of current smoking status with APE1 Asp148Glu polymorphism was found. These results suggest that the presence of one or two APE1 Glu allele was associated with the risk of developing lung cancer.

Bladder cancer and polymorphisms of DNA repair genes (XRCC1, XRCC3, XPD, XPG, APE1, hOGG1).

Carcinogenic molecules from cigarettes are known to cause DNA damage to bladder epithelial cells, but such damage can be corrected by some DNA repair mechanisms such as base and nucleotide excision repair, double-strand repair and mismatch repair. Various gene products play a role in these DNA repair systems. The aim of this study was to investigate six of these genes (XRCC1, XRCC3, XPD, XPG, APE1, hOGG1) each of which has a separate role in these repair mechanisms. The study was performed on 83 bladder cancer patients and 45 healthy controls. The genes were amplified by polymerase chain reaction (PCR) and restriction fragment polymorphism determinations were used to elucidate the specific changes in the gene region. There was no difference in smoking status between patient and control groups. It was found that there was a statistical significance in XRCC3 T carriers between patient and control groups and so there was a 4.87-fold protective role by the XRCC3 T allele against bladder cancer. The AA genotype and A allele carriers of the APE gene were more frequent in the transitional epithelial carcinoma group than in the adenocarcinoma group. The genotype distribution for the APE gene was determined to be significantly different between local and invasive cases; G allele carriers for this gene were significantly higher in invasive cancer types.

ARE-I polymorphism on PSA gene in prostate cancer patients of a Turkish population.

BACKGROUND: The gene for kallikrein-like serin protease, prostate-specific antigen (PSA), has been a candidate gene in several studies. It is known that androgens are important in the proliferation and development of prostate gland and they are the main regulators of PSA expression. The polymorphism of the ARE-I locus on the PSA gene was studied in prostate cancer patients to determine a possible relationship of that locus to prostate cancer risk. PATIENTS AND METHODS: Forty-nine prostate cancer patients and forty-seven healthy control subjects were compared. Total and free PSA levels were measured by an enzymatic immunoassay method. PSA ARE-I polymorphism analyses were performed using a previously described PCR-restriction fragment length polymorphism (RFLP) method. RESULTS: There were no significant differences between the control and patient groups for any of the PSA-AREI genotypes, but the G allele carriers had a 2-fold higher risk of developing advanced prostate cancer. CONCLUSION: G allele carriers have a higher risk of developing advanced prostate cancer. With further research, such PSA-AREI polymorphism analyses may help in follow-up and in deciding the prognosis of prostate cancer patients.

The relationship of oral disturbances of diabetes mellitus patients with paraoxonase gene polymorphisms.

Diabetes Mellitus (DM) is a multisystemic disorder with serious complications and these patients may also have serious problems with their oral cavity probably because of the microangiopathic and neuropathic complications. In diabetic patients, there may be several problems of the oral cavity such as gingivitis, periodontitis, candidiasis, glossitis, oral ulcerations, loss of taste sensations, opportunistic infections and several other conditions dependent on these. One of the recent theories about complications in DM is the contribution of reactive oxygen radicals. Paraoxonase (PON1) is an enzyme that is synthesized in liver and having the capability of hydrolasing the active metabolite of an insectisid, parathion. Previously it was shown that there are two polymorphic areas on the PON1 gene: one causing a Leu --> Met substitution at 55th position, the other causing Gln --> Arg at the 192nd position. We investigated the differences in PON activities related to the oral lesions in Type 2 diabetics and control subjects to see their relationships with PON1 activity levels and the two main gene polymorphisms of PON1 genes, PON1 192 and PON1 55. We had 51 patients and 53 healthy subjects used in the study. PON activity was significantly decreased in Type 2 DM group compared to the control group. Neither PON1 192 nor PON1 55 genotypes had any differential effect on PON1 enzyme activity levels in either group. However, we found that PON1 55 M allele carriers had greater risk for general periodontal and/or gingival problems.

Relationship between interleukin-8 and the oxidant-antioxidant system in end-stage renal failure patients.

OBJECTIVES: We aimed to evaluate the relationship between interleukin-8 and the oxidant-antioxidant system in end-stage renal failure patients with and without diabetes mellitus undergoing regular hemodialysis treatment. MATERIALS AND METHODS: Plasma levels of malondialdehyde and whole blood reduced glutathione were measured as markers of the oxidant and antioxidant systems, respectively. Plasma interleukin-8 levels were measured by enzyme-linked immunosorbent assay. RESULTS: When compared with controls, plasma interleukin-8 levels were elevated in both diabetic and nondiabetic end-stage renal disease patients. Plasma malondialdehyde levels were statistically significantly higher in end-stage renal disease patients with and without diabetes mellitus than they were in controls; however, reduced glutathione levels were statistically significantly lower in diabetic and nondiabetic end-stage renal disease patients than they were controls. CONCLUSIONS: In end-stage renal disease patients with and without diabetes mellitus, elevated interleukin- 8 levels and decreased reduced glutathione levels may be attributed to increased oxidative stress due to inflammation. In other words, increased reactive oxygen species may induce interleukin-8 production and result in diminished reduced glutathione levels. Our data suggest a relationship between interleukin- 8 and the oxidant-antioxidant system in end-stage renal failure patients.

Methylenetetrahydrofolate reductase C677T polymorphism in patients with gastric and colorectal cancer.

This study was designed to investigate, in the Turkish population, an association of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and the risk of gastric and colorectal cancer. Our study was carried out in 35 patients with gastric cancer (20 men, 15 women) and 144 controls (75 men, 69 women) and 52 colorectal cancer (31 men, 21 women). MTHFR C677T genotypes were determined by polymerase chain reaction, restriction fragment length polymorphism techniques. No differences were observed in the distribution of MTHFR genotypes or allele frequencies in cases versus controls. The homozygous mutation (T/T) in the MTHFR gene was identified in 14.3% of gastric cancer versus 10.4% of controls. MTHFR C677T frequencies of the CC, CT and TT genotypes among colorectal cancer patients were 34.6%, 51.9% and 13.5%, respectively. MTHFR C677T polymorphism may not be important in an individual's susceptibility to gastric and colorectal cancer in Turkey and may not be a useful marker for identifying patients at high risk of developing gastric and colorectal cancer.

Is paraoxonase 192 gene polymorphism a risk factor for membranoproliferative glomerulonephritis in children?

We investigated the effects of paraoxonase (PON1) 192 polymorphism on serum PON1 activity and the impact of phenotypic expression on the risk and prognosis of Turkish children with membranoproliferative glomerulonephritis (MPGN). Eighteen children with biopsy-proven Type I MPGN (10 boys, 8 girls) and age-matched 53 healthy controls were included in the study. PCR (polymerase chain reaction), RFLP (restriction fragment length polymorphism) and agarose gel electrophoresis techniques were used to determine the PON1 192 genotype. PON1 activity was measured by spectrophotometric assay of p-nitrophenol production following addition of paraoxon. We found that PON1 192 genotype distribution (AA, AB, BB) in MPGN patients were 61.1%, 22.3%, 16.6% and 15.1%, 35.8%, 49.1% in controls, respectively. The frequency of AA genotypes was significantly higher in the MPGN group (0.611) compared with the healthy controls (0.151) (p < 0.001). Although the serum PON1 activity was lower in MPGN patients (103.3 +/- 55.2 U/l) than the healthy controls (130.9 +/- 71.2 U/mol), the difference was not statistically significant (p = 0.0563). In the genotypes of patients and controls classified according to PON1 A/B polymorphism; serum PON1 activities were significantly increased (p < 0.001, ANOVA) in the order of PON1 AA, AB and BB in both MPGN patients (82.4, 91.7 and 173.6 U/l) and healthy controls (85.9, 119.9 and 193.1 U/l), respectively. There was a significant relationship between the poor prognosis and having AA genotype and low PON1 activity. Of the 8 patients with poor prognosis, 7 had genotype AA and the remaining one was AB heterozygote. Our results suggest that homozygosity for the A allele might have an important role on the risk for developing MPGN and may also be associated with the poor prognosis of disease. In conclusion, we suggest that the PON1 activities are affected by PON1 genetic variability in Turkish patients with MPGN.

Paraoxonase 1 192 and 55 polymorphisms in nephrotic children.

Human paraoxonase 1 (PON1) is a serum enzyme related to high-density lipoprotein which has a major role in preventing oxidative modification of low-density lipoprotein. Due to its amino acid substitution PON1 has two genetic polymorphisms. These polymorphisms are characterized by the location of glutamine (A genotype) and arginine (B genotype) at position 192, and leucine (L genotype) and methionine (M genotype) at position 55. Hyperlipidemia and increased lipid oxidation in nephrotic syndrome may lead to glomerulosclerosis and progression of the glomerular disease. In this study we aimed to investigate PON1 192 and PON1 55 polymorphisms in children with focal segmental glomerulosclerosis (FSGS) and control subjects. The study included 25 children with biopsy-proven FSGS and 30 healthy controls. We demonstrated a statistically significant difference between FSGS patients and control subjects with respect to the distribution of the PON1 polymorphism. The AA genotype was less frequent and the AB+BB genotype was more frequent in FSGS patients than in controls (48 versus 73% for AA genotype and 52 versus 27% for AB+BB genotype, p<0.05). Distributions of PON1 55 genotypes of FSGS and control subjects were also statistically different (76 versus 43% for LL genotype and 24 versus 57% for LM+MM genotype, p<0.05) (case-control study, dominant model, Fisher's exact test). The distributions of both genotypes in subgroups of FSGS (stable renal function versus declining renal function) were not statistically different. We conclude in this preliminary study that presence of B allele and/or L allele may be risk factors for the development of FSGS in children.