Polymorphisms in Turkish population » University

The relationship between paraoxanase gene Leu-Met (55) and Gln-Arg (192) polymorphisms and coronary artery disease

admin — Thu, 25 Feb 2010 20:06:25 +0000

Turk Kardiyol Dern Ars. 2009 Oct;37(7):473-8.

Taşkiran P, Cam SF, Sekuri C, Tüzün N, Alioğlu E, Altintaş N, Berdeli A.

Department of Medical Biology and Genetics, Medicine Faculty of Celal Bayar University, Manisa, Turkey.

OBJECTIVES: Paraoxonase (PON1) is a high-density lipoprotein (HDL)-associated esterase that hydrolyses lipoperoxides. PON1 serves as a protective factor against oxidative modification of LDL, suggesting that it may play an important role in the prevention of atherosclerotic process. Research has focused on two polymorphisms: leucine (L allele) to methionine (M allele) substitution at codon 55, and glutamine (A allele) to arginine (B allele) substitution at codon 192. STUDY DESIGN: We examined amino acid changes at codon 55 and 192 in the PON1 gene by polymerase chain reaction and using restriction enzymes in 120 patients (92 men, 28 women; mean age 48.2+/-4.3 years) with premature coronary artery disease (CAD) and in 102 healthy subjects (80 men, 22 women; mean age 46.8+/-5.2 years) with no history of CAD and a normal electrocardiogram. RESULTS: Distribution of genotypes in the patient and control groups at codon 55 were 6.7% and 4.9% for MM, 46.7% and 29.4% for LM, 46.7% and 65.7% for LL, respectively. The frequency of genotypes at codon 192 were as follows: 4.2% and 2% for RR, 40% and 35.3% for QR, and 55.8% and 62.8% for QQ, respectively. While the frequency of PON1 55M allele was higher in the CAD group (0.3 vs. 0.2), PON1 192R allele frequency did not differ (p>0.05). There was a significant relationship between the PON1 M/L55 polymorphism and CAD (p=0.017), whereas the R/Q192 polymorphism was not associated with CAD (p=0.445). CONCLUSION: These data suggest that the PON1 M/L55 polymorphism shows a significant relationship with CAD and the Q/R192 polymorphism is not a major risk factor causing susceptibility to CAD in our population.

TNF-alpha promoter polymorphisms in multiple sclerosis: no association with -308 and -238 alleles, but the -857 alleles in associated with the disease in Turkish patients.

admin — Thu, 25 Feb 2010 20:04:13 +0000

Akcali A, Pehlivan S, Pehlivan M, Sever T, Akgul P, Neyal M.

Department of Neurology, Gaziantep University School of Medicine, Gaziantep, Turkey.

Summary Dysregulation in the expression of pro- and anti-inflammatory cytokines is one of the milestones in multiple sclerosis (MS) development and progression. Tumour necrosis factor (TNF-alpha), a proinflammatory cytokine is believed to play an important role in MS pathogenesis. The objective of this study is to investigate the association between TNF-alpha promoter region (TNF-alpha-238, -308 and -857) and susceptibility to MS and clinical course of the disease. Eighty-six relapsing remitting MS patients and 150 sex-, age- and ethnic-matched controls were enrolled in the study. Genotyping was performed by PCR-RFLP method. We observed a statistically significant increase in TNF-alpha 857 CC genotype in MS patients than controls (P < 0.001) while TNF-alpha 857 CT genotype showed a significant negative correlation with MS patients (P = 0.033). No differences in the distribution of the TNF-alpha-238 and -308 alleles were observed. None of the three polymorphisms (-238, -308 and -857) did not show relation with disease duration, Expanded Disability Status Scale or age of onset. On the other hand, significant difference of TNF -857 CC genotype was identified with the low disease index (P = 0.025). Although the study group is small, the results indicate that TNF-alpha 857 CC genotype may cause susceptibility to MS in the Turkish population.

Association between mannose-binding lectin levels and gene polymorphisms in chronic periodontitis and response to treatment.

admin — Thu, 25 Feb 2010 20:02:02 +0000

Arch Oral Biol. 2010 Feb 2.

Ozçaka O, Bıçakcı N, Nalbantsoy A, Köse T, Berdeli A.

Department of Periodontology, School of Dentistry, University of Ege, Izmir, Turkey.

BACKGROUND: The aims of the present study were: (1) to investigate mannose-binding lectin (MBL) gene exon-1 polymorphisms in Turkish subjects with chronic periodontitis (CP), (2) to assess the association between these polymorphisms and plasma MBL levels, (3) to determine the effects of MBL genotypes on the outcomes of non-surgical periodontal therapy. METHODS: A total of 172 subjects were included in the present study. Genomic DNA was obtained from the peripheral blood of 83 CP patients and 89 periodontally healthy subjects. The MBL levels were measured by enzyme-linked immunosorbent assay (ELISA). The MBL gene exon-1 polymorphisms were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: Subjects homozygous for the frequent allele A had higher MBL plasma levels compared with rare allele B carriers. This difference in MBL plasma levels was statistically significant both in CP patients and healthy subjects. The distribution of MBL gene codon 54 genotypes and allele frequencies did not differ significantly between study groups. All study subjects were the MBL gene codon 52 and 57 frequent allele A carriers. Codon 54 B allele carriers had similar clinical periodontal parameters compared with AA genotypes after non-surgical periodontal therapy. CONCLUSIONS: The present study failed to find any significant association between the MBL gene codon 54 polymorphisms and severe CP in a Turkish population. MBL gene rare allele carriers had lower MBL plasma levels in both study groups. It seems that MBL gene codon 54 B allele carriage may not influence the outcome of periodontal therapy. Copyright © 2010. Published by Elsevier Ltd.

677C>T and 1298A>C Polymorphisms of Methylenetetrahydropholate Reductase Gene and Biochemical Parameters in Turkish Population with Spina Bifida Occulta.

admin — Fri, 05 Feb 2010 20:40:10 +0000

Turk Neurosurg. 2010 Jan;20(1):9-15.

Eser B, Cosar M, Eser O, Erdogan MO, Aslan A, Yildiz H, Boyaci G, Buyukbas S, Solak M.

Selcuk University, Meram Faculty of Medicine, Department of Medical Genetics, Konya, Turkey.

AIM: This study aimed to investigate the 677C > T and 1298A > C MTHFR gene polymorphisms and their metabolic effects on the levels of folate, vitamin B12 and homocysteine in the serum of Turkish spina bifida occulta (SBO) patients and healthy individuals in disease. MATERIAL and METHODS: A case-control study was performed to detect 677C > T and 1298A > C MTHFR gene polymorphisms in 39 SBO patients and 34 healthy individuals. The folate, vitamin B12 and homocysteine concentrations in the serum of SBO and healthy individuals were evaluated and compared with MTHFR gene polymorphisms. RESULTS: 677 CC/CT/TT MTHFR genotype frequency differences between the SBO patients and controls were not significant (x(2)=3.325, P=0.068; x(2)=1.479, P=0.224; x(2)=0.275, P=0.600; respectively). 1298A > C MTHFR genotype frequency differences between the SBO patients and controls were significant (x(2)=8.477, P=0.004). The frequencies of the Aand C alleles of the 1298A > C polymorphism did not differ in a statistically significant manner between the groups (x(2)=0.576, P=0.448). The biochemical parameters were not significantly different between SBO patients and healthy individuals (P > 0.05). CONCLUSION: The 677C > T and 1298A > C polymorphisms of the MTHFR gene cannot be regarded as major risk factors for SBO in the Turkish patients 677TT homozygosity may affect the metabolism of homocysteine.

Angiotensin-Converting Enzyme Gene Polymorphism in Overweight and Obese Turkish Patients with Insulin Resistance.

admin — Fri, 05 Feb 2010 20:37:16 +0000

DNA Cell Biol. 2010 Jan 13.

Akin F, Turgut S, Bastemir M, Turgut G, Kursunluoglu R, Karasu U, Guclu A.

1 Department of Endocrinology and Metabolism, Faculty of Medicine, Pamukkale University , Denizli, Turkey .

The aim of this study was to analyze the distribution of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in obese Turkish patients with insulin resistance (IR). Sixty-two obese Turkish patients with IR were enrolled in this study. One hundred healthy people without IR were recruited as the control group. ACE amplification was performed by polymerase chain reaction. The frequency of the DD genotype was significantly higher in obese patients with IR than in control subjects. Of sixty-two patients, 1 (1.6%) had an II genotype, 22 (35.5%) had an ID genotype, and 39 (62.9%) had a DD genotype. The frequency of the I allele in the patient group was significantly lower than in controls. We found that the frequency of the DD genotype was higher in obese Turkish patients with IR. ACE gene I/D polymorphism may be associated with obesity in the Turkish population.

Genetic Variations in the Hypoxia-inducible Factor-1{alpha} Gene and Lung Cancer.

admin — Mon, 24 Aug 2009 20:47:00 +0000

Exp Biol Med (Maywood). 2009 Jun 22.

Konac E, Dogan I, Onen IH, Yurdakul AS, Ozturk C, Varol A, Ekmekci A.

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.

CTLA-4 gene polymorphism of exon 1(+49 A/G) in Turkish systemic lupus erythematosus patients.

admin — Mon, 24 Aug 2009 20:44:32 +0000

Int J Immunogenet. 2009 Aug;36(4):245-50

Ulker M, Yazisiz V, Sallakci N, Avci AB, Sanlioglu S, Yegin O, Terzioglu E.

Akdeniz University Teknocity, Kampus Antalya, Turkey.

Cytotoxic T lymphocyte-associated antigen-4 is a cell-surface molecule providing a negative signal for T cell activation. CTLA-4 gene polymorphisms are known to be related with genetic susceptibility to various autoimmune diseases, including systemic lupus erythematosus (SLE). However, the effects of this polymorphism on clinical features of SLE have not been defined. We analysed the CTLA-4 gene +49 A/G polymorphisms in patients with SLE by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and investigated the effect of polymorphisms on clinical outcomes. Blood was collected from 47 unrelated Turkish SLE patients, all fulfilling the American College of Rheumatology criteria for SLE, and 100 ethnically matched healthy volunteers. The AA genotype was a predominant genotype in the Turkish population and genotype frequencies of CTLA-4 AA were significantly higher in SLE patients (70%) than healthy controls (47%) (P = 0.015). There was a statistically significant difference in the AA genotype [odds ratio (OR): 2.66, confidence interval (CI) 95%: 1.27-5.56, P = 0.014] distribution among patients and controls. There was also an increase in A allele frequency in SLE and controls, but the difference was not statistically significant (81% vs. 70%, P = 0.068, OR = 1.8, CI 95%: 0.99-3.28). Interestingly, mean age and mean age of onset disease was higher in AA homozygote SLE patients compared to non-AA (39.2 +/- 11.5 vs. 31.6 +/- 10.6, P = 0.044; 32.38 vs. 24.31, P = 0.046, respectively). There was no association between genotype and the other clinical features of SLE. Our results suggested that CTLA-4 +49 AA genotype might be a risk factor for the development of SLE in Turkish population and G allele might be involved in early development of SLE. No association with clinical features was found for polymorphism of the promoter region in CTLA-4 +49.

Association of beta-1 and beta-2 adrenergic receptor gene polymorphisms with myocardial infarction.

admin — Mon, 24 Aug 2009 20:41:52 +0000

Yilmaz A, Kaya MG, Merdanoglu U, Ergun MA, Cengel A, Menevse S.

Department of Medical Biology and Genetics, Faculty of Medicine, Gazi University, Besevler, Ankara, 06510, Turkey. akinyilmaz@gazi.edu.tr

Both beta(1)- and beta2-adrenergic receptors (beta(1)- and beta(2)-AR) have important roles in heart function mainly in response to catecholamines. Some specific polymorphisms in the beta(1)- and beta(2)-AR genes, named ADRB1 and ADRB2, respectively, have been implicated in several cardiovascular and noncardiovascular phenotypes. In this study, we aimed to investigate the possible relationship between Ser49Gly and Arg389Gly polymorphisms of the ADRB1 and Arg16Gly and Gln27Glu polymorphisms of the ADRB2 gene with ST elevation myocardial infarction (MI) in a Turkish population. One hundred patients with ST elevation MI and 100 healthy control subjects were genotyped using the PCR-RFLP method. Although the Arg389 allele of the ADRB1 gene was associated with an elevated risk of MI, the Glu27 allele of the ADRB2 gene was associated with a decreased risk of MI. Carriers of the ADRB1 Arg389 allele (heterozygotes+homozygotes) had an approximately 3.5-fold increased risk for MI than Gly389 homozygotes (OR=3.59, 95% CI=0.96-13.47, P=0.045). For the ADRB2 Gln27Glu polymorphism, subjects having one or two copies of the Glu27 allele showed a decreased risk of MI compared with Gln27 homozygote subjects (OR=0.48, 95% CI=0.24-0.94, P=0.03). Haplotype analysis of these polymorphisms showed no significant differences between groups. These results suggest that the Arg389Gly and Gln27Glu polymorphisms may be associated with an altered risk of MI in this Turkish population.

The clinical significance of parathyroid tissue calcium sensing receptor gene polymorphisms and expression levels in end-stage renal disease patients.

admin — Mon, 24 Aug 2009 20:40:18 +0000

Clin Nephrol. 2009 Aug;72(2):114-21.

Eren PA, Turan K, Berber I, Canbakan M, Kara M, Tellioglu G, Bugan U, Sevinç C, Turkmen F, Titiz MI.

1Departments of Molecular Genetics and 3Transplantation, Haydarpasa Numune Research and Training Hospital, and 2Department of Basic Sciences, Faculty of Pharmacy, Marmara University, Istanbul, Turkey.

Background: The calcium sending receptor (CaSR) allows parathyroid and kidney tubular cells to regulate PTH secretion and tubular calcium reabsorption. In the present report, we examined the relationship between CaSR gene polymorphisms and parathyroid CaSR expression and serum calcium/parathyroid hormone (PTH) levels and clinical progress in ESRD patients in the Turkish population. Methods: We genotyped the CaSR R990G and Q1011E variants in 192 end-stage renal disease (ESRD) patients by allele-specific PCR. CaSR expression in parathyroid tissues of operated 33 patients was quantified with quantitative reverse transcription-PCR. Results: Compared with other genotypes, the ratio of both codon 990-AA and 1011-CC polymorphisms was found higher in operated patients (p = 0.001). In the total patient group PTH levels were found higher in patients with CC1011 genotype than those with CG1011 (1015.15 +/- 925.41 pg/ml; 523.84 +/- 544.6 pg/ml, respectively, p = 0.002). There were statistically important higher Ca2+ levels in the AA990 allele carrying cases than AG990 positive ones (9.3 +/- 1.0 mg/dl vs. 8.8 +/- 0.9, p = 0.006). On the other hand, the expression of CaSR in parathyroid tissue was found inversely proportional with serum PTH level (r = -0.71). Conclusion: Present data suggest that co-presence of CaSR gene AA990 and CC1011 alleles is a possible risk factor for bad prognosis in secondary hyperparathyroidism. Patients carrying this genotype have tendency to require operation early in their medical therapy period and need postoperative close follow up for possible recurrences.

Influence of genetic polymorphisms, smoking, gender and age on CYP1A2 activity in a Turkish population.

admin — Sun, 12 Jul 2009 06:20:28 +0000

Pharmacogenomics. 2009 May;10(5):769-78.

Gunes A, Ozbey G, Vural EH, Uluoglu C, Scordo MG, Zengil H, Dahl ML.Department of Medical Sciences, Clinical Pharmacology, Uppsala University, Uppsala, Sweden. Arzu.Gunes@medsci.uu.se

AIMS: To study the variation in CYP1A2 activity in relation to smoking, gender, age and CYP1A2 polymorphisms. MATERIALS & METHODS: CYP1A2 activity was determined by plasma paraxanthine:caffeine ratio (17X:137X) 4 h after the intake of a standardized cup of coffee in 146 Turkish healthy volunteers. Seven CYP1A2 polymorphisms (-3860G>A, -3113G>A, -2467del/T, -739T>G, -729C>T, -163C>A and 5347T>C) were analyzed. RESULTS: The 17X:137X ratios were increased in smokers (p < 0.0001) and tended to be higher in men both among nonsmokers (p = 0.051) and smokers (p = 0.064). Age-related differences were observed only among nonsmoking women (p = 0.024). The -163C>A polymorphism correlated with 17X:137X ratios only in smokers (p = 0.006). Furthermore, increased 17X:137X ratios were observed in CYP1A2 haplotype H4 (-3860G, -3113G, -2467del, -739T, -729C, -163A and 5347T) carriers in the overall study population (p = 0.026). Multiple regression analyses including smoking, gender, -163C>A genotype and age revealed a significant influence of smoking (p < 0.0001) and gender (p = 0.002) in the overall study population. However, in nonsmokers only the influence of gender remained significant (p = 0.021), while in smokers the influence of the -163C>A genotype held the statistical significance (p = 0.019). The influence of haplotype H4 remained significant (p = 0.028) in the overall study population in similar analyses. CONCLUSION: Smoking has the strongest impact on CYP1A2 activity, while gender and haplotype H4 showed marginal effects. The influence of the -163C>A polymorphism on CYP1A2 activity in smokers suggests an effect on the inducibility of the enzyme.