Bioequivalence study of two favipiravir tablet formulations in healthy male subjects.

OBJECTIVE: The global pandemic called COVID-19 has dragged the world into a healthcare crisis, and favipiravir is one of the most prescribed agents against the virus so far. Favipiravir is a repurposed antiviral agent in treatment of SARS-CoV-2 infection, and to meet the current need, pharmaceutical companies are working for manufacturing licensed generic favipiravir. For getting the marketing authorization, the bioequivalence of the generic product must be proven first. The aim of this study is to demonstrate the bioequivalence of a new favipiravir tablet formulation as compared to the reference tablet formulation in healthy male subjects under fasting conditions. MATERIALS AND METHODS: To prove the bioequivalence, a randomized, single oral dose, cross-over, two-period study was carried out in 30 healthy subjects under fasting conditions. Plasma favipiravir levels were quantified by using an in-house-developed high performance liquid chromatography with mass spectrometry detector (LC-MSD) method. RESULTS: The 90% CIs for the test/reference geometric mean ratios of the Cmax and AUC0-tlast were 88.02 - 103.11% and 98.19 - 102.06%, respectively. CONCLUSION: This single-dose study has shown that the test and reference favipiravir products met the required bioequivalence criteria. Besides, both products were well tolerated and safe.

The role of endothelial nitric oxide synthase gene polymorphisms in patients with lung cancer.

OBJECTIVES: Lung cancer is a disease characterized by uncontrolled cell growth in the lung tissues. The most common causes of lung cancer include smoking, exposure to radon gas, asbestos, environmental pollutants as well as genetic factors. Nitric oxide (NO) has potential mutagenic and carcinogenic activity and may play an important role in lung cancer. Endothelial NO, synthesized from L-arginine by endothelial NO synthase (eNOS), inhibits apoptosis and promotes angiogenesis and tumor cell proliferation. The aim of the present study was to examine the possible relationship between eNOS gene intron 4 variable number of tandem repeat (VNTR) and exon 7-G894T (Glu298Asp) polymorphisms and lung cancer risk. METHODS: DNA was extracted from peripheral blood leukocytes of 107 lung cancer patients and 100 control subjects. Designated polymorphisms were identified by polymerase chain reaction (PCR) and/or restriction fragment length polymorphism (RFLP). RESULTS: Our study showed that the frequencies of the b/b genotype and b allele of eNOS gene intron 4 VNTR polymorphism were significantly higher in lung cancer patients than in controls (P < 0.05). However, there was no significant association between eNOS gene G894T polymorphism and lung cancer risk (P > 0.05). CONCLUSION: These results suggest that the presence of the intron 4 VNTR* b allele and b/b genotype may be a genetic risk factor for development of lung cancer. Further larger-scale studies are needed to confirm these findings.

Association of melatonin receptor 1 B gene (rs10830963 and rs9192552) polymorphism with adolescent obesity and related comorbidities in Turkey.

Objective To examine the role of rs10830963 and rs8192552 polymorphisms in melatonin receptor 1 B (MTNR1B) gene on the development of obesity and related comorbidities among adolescents in South-Eastern Turkey. Methods The present study included 200 unrelated adolescents (100 obese, 100 normal weight). The rs8192552 and rs10830963 polymorphisms in the MTNR1B gene were genotyped using a PCR SNaPshot assay. Results No statistically significant association was observed between MTNR1B gene rs8192552/rs10830963 polymorphisms and adolescent obesity. In adolescents with an rs8192552 E allele, homeostasis model assessment for insulin resistance (IR) level was lower and IR was less common. In morbidly obese adolescents with an rs8192552 E allele, total cholesterol level was lower. In obese adolescents with metabolic syndrome, plasma fasting glucose level was higher in rs10830963G allele carriers. In obese girls, body weight was lower in those with a rs10830963 C allele, whereas in obese boys, body weight and waist circumference were higher in those with a rs10830963 C allele. Conclusions The MTNR1B gene was not confirmed as an obesity susceptibility gene in adolescents. However, an association between the MTNR1B gene and IR/hypercholesterolemia/metabolic syndrome was observed in obese adolescents. A sex-specific effect on obesity was also identified.

Adolescent obesity and the role of the fat mass and obesity-associated gene polymorphism.

PURPOSE: The association between fat mass and obesity-associated (FTO) gene and obesity is unclear in both adults and adolescents. The aim of this study was to examine the role of the FTO gene variant rs9939609 as a candidate gene for obesity and the relationship between insulin resistance (IR), metabolic syndrome (MetS), estimated glomerular filtration rate (eGFR) and neutrophil-to-lymphocyte ratio (NLR). METHODS: Obese adolescents (n=100) and healthy controls (n=100) were included. Rs9939609 polymorphism in the FTO gene was genotyped by PCR-SNaPshot. RESULTS: The prevalence of insulin resistance (IR), metabolic syndrome (MetS) and hyperfiltration were 47%, 60% and 27%, respectively. There were no significant differences in genotype and allele frequencies between obese adolescents and controls; however, prevalence of MetS in female patients with A allele carriers was more frequent and prevalence of hyperfiltration was less frequent with T allele carriers (P.

An Information Theoretical Study of the Epistasis Between the CNR1 1359 G/A Polymorphism and the Taq1A and Taq1B DRD2 Polymorphisms: Assessing the Susceptibility to Cannabis Addiction in a Turkish Population.

Addiction is a complex, multi-factorial disease, and thus, analyzing genetic variants at multiple loci and gene-gene interactions among them (epistasis) can provide crucial clues about causative factors of addiction which cannot be detected with single-nucleotide polymorphism (SNP) association studies. In this study, we discuss the interaction between the 1359 G/A polymorphism of the CNR1 gene and the DRD2 gene polymorphisms and the net effect of any possible epistasis on the cannabis addiction phenotype in a Turkish population. Using bivariate synergy and mutual information concepts as a means of capturing the magnitude of interaction between marker pairs, the present study not only confirms the A1 marker allele as a risk factor but also reveals a finer-grained association between A and B markers which manifests itself both as a preventive and a risk factor. Our results indicate that the increased phenotype of cases require an individual to be either heterozygous at both loci or homozygous at locus B with homozygous risk factor A1A1 present. We hypothesize that overlapping expressions of CB1 and D2R is the cause of CB1-D2R interactions in cases of substance abuse and the different polymorphisms of CNR1 and DRD2 genes may have decisive roles in the nature of these interactions in terms of promoting or alleviating the cannabis addiction risk factor of the individual.

Bernard Lerer: recipient of the 2014 inaugural Werner Kalow Responsible Innovation Prize in Global Omics and Personalized Medicine (Pacific Rim Association for Clinical Pharmacogenetics).

This article announces the recipient of the 2014 inaugural Werner Kalow Responsible Innovation Prize in Global Omics and Personalized Medicine by the Pacific Rim Association for Clinical Pharmacogenetics (PRACP): Bernard Lerer, professor of psychiatry and director of the Biological Psychiatry Laboratory, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. The Werner Kalow Responsible Innovation Prize is given to an exceptional interdisciplinary scholar who has made highly innovative and enduring contributions to global omics science and personalized medicine, with both vertical and horizontal (transdisciplinary) impacts. The prize is established in memory of a beloved colleague, mentor, and friend, the late Professor Werner Kalow, who cultivated the idea and practice of pharmacogenetics in modern therapeutics commencing in the 1950s. PRACP, the prize's sponsor, is one of the longest standing learned societies in the Asia-Pacific region, and was founded by Kalow and colleagues more than two decades ago in the then-emerging field of pharmacogenetics. In announcing this inaugural prize and its winner, we seek to highlight the works of prize winner, Professor Lerer. Additionally, we contextualize the significance of the prize by recalling the life and works of Professor Kalow and providing a brief socio-technical history of the rise of pharmacogenetics and personalized medicine as a veritable form of 21(st) century scientific practice. The article also fills a void in previous social science analyses of pharmacogenetics, by bringing to the fore the works of Kalow from 1995 to 2008, when he presciently noted the rise of yet another field of postgenomics inquiry--pharmacoepigenetics--that railed against genetic determinism and underscored the temporal and spatial plasticity of genetic components of drug response, with invention of the repeated drug administration (RDA) method that estimates the dynamic heritabilities of drug response. The prize goes a long way to cultivate transgenerational capacity and broader cognizance of the concept and practice of responsible innovation as an important criterion of 21(st) century omics science and personalized medicine. A new call is presently in place for the 2016 PRACP Werner Kalow prize. Nominations can be made in support of an exceptional individual interdisciplinary scholar, or alternatively, an entire research team, from any region in the world with a record of highly innovative contributions to global omics science and/or personalized medicine, in the spirit of responsible innovation. The application process is straightforward, requiring a signed, 1500-word nomination letter (by the applicant or sponsor) submitted not later than May 31, 2015.

Mitochondrial uncoupling protein 2 (UCP2) gene polymorphisms are associated with childhood obesity and related metabolic disorders.

OBJECTIVE: This study aimed to investigate the possible role of uncoupling protein 2 (UCP2) gene polymorphisms in childhood obesity and related metabolic disorders. METHODS: Obese patients (n=100) and healthy controls (n=100) were analyzed for -866G>A and insertion/deletion (I/D) polymorphisms of the UCP2 gene by polymerase chain raction and/or restriction fragment length polymorphism. RESULTS: UCP2 I/D polymorphism showed an association with obesity. The insertion homozygous genotype (II) was higher in obese patients (p=0.0001), while the DD genotype was higher in controls (p=0.0034). Body mass index and relative weight were lower in patients carrying the A allele of the -866G>A polymorphism (p=0.021 and p=0.047, respectively). There was an association between insulin resistance and -866A allele carrier patients with consanguineous parents (p=0.005). CONCLUSION: Insertion homozygous genotype and the allele of I/D polymorphism were found to be risk factors for childhood obesity and related metabolic disorders. The -866A allele was associated with susceptibility to central adiposity, hypercholesterolemia, hypertriglyceridemia and insulin resistance.

Childhood obesity and the role of dopamine D2 receptor and cannabinoid receptor-1 gene polymorphisms.

AIMS: The dopaminergic and endocannabinoid systems are involved in regulation of feeding behavior. The aim of the study is to examine the possible relation between polymorphisms of the dopamine D2 receptor (DRD2) and cannabinoid receptor-1 (CNR1) genes and childhood obesity. METHODS: A hundred obese children and 100 healthy controls were analyzed for DRD2 Taq1A and Taq1B and CNR1 1359G/A polymorphisms. Genotyping was performed by polymerase chain reaction and restriction fragment length polymorphism. RESULTS: There were no statistically significant differences in DRD2 Taq1A and DRD2 Taq1B genotypes or allelic frequencies between obese children and controls (p>0.05). In patients with Taq1B2 allele, morbid obesity was less frequent (p=0.010). The frequency of the A allele of CNR1 1359G/A polymorphism was significantly higher in obese children than in controls (21.0% vs. 13.0%, p=0.0166). The frequency of genotypes AG and GG of the CNR1 1359G/A SNP was different between obese children and control subjects (for AG: 34.0% vs. 22.0%, p=0.0294; for GG: 62.0% vs. 76.0%, p=0.0162, respectively). CONCLUSIONS: No significant difference was found between genotypes and alleles of DRD2 Taq1A and DRD2 Taq1B polymorphism in patients and controls, while the CNR1 receptor 1359G/A polymorphism and the presence of the A allele may be one risk factor for susceptibility to obesity.

Analysis of dopamine D2 receptor (DRD2) gene polymorphisms in cannabinoid addicts.

The gene encoding the dopamine D2 receptor (DRD2) has been suggested as a candidate gene for substance dependence. In this study, the possible association between Taq1A and Taq1B DRD2 polymorphisms and cannabinoid dependence was investigated. One hundred and twelve cannabinoid addicted and 130 healthy control subjects were included in this study. The Taq1A and Taq1B genotypes were determined in all subjects by polymerase chain reaction. For each polymorphism (A or B), the subjects were categorized into three groups according to their genotype, that is, the subjects with alleles A1/A1, A1/A2, A2/A2; B1/B1, B1/B2, and B2/B2. A significant association was found between Taq1A gene polymorphism and cannabinoid addicts compared to the control subjects. This finding suggests that polymorphism of the Taq1A, but not the Taq1B, may be associated with the susceptibility to cannabinoid dependence. Further clinical studies are required to be carried out for confirmation and evaluation of these findings.

Association of angiotensin converting enzyme gene insertion/deletion polymorphism with lung cancer in Turkey.

Angiotensin-converting enzyme (ACE) plays an important role in the physiological control of blood pressure and inflammation. We investigated an insertion/deletion (I/D) polymorphism of the gene for ACE in relation to cardiovascular, cerebrovascular, neurodegenerative, and inflammatory diseases. The purpose of the present study was to investigate a possible association between lung cancer and insertion/deletion polymorphism of the ACE gene. A total of 125 patients with lung cancer and 165 control subjects were enrolled in the present study. ACE I/D genotypes were determined by polymerase chain reaction. Allelic frequencies and genotype distribution of the ACE I/D polymorphism in the patient group were significantly different from control subjects (ACE II genotype 29.6 vs. 17.6%, P = 0.011; ACE I allele 49.6 vs. 39.4%, P =0.009). Our data suggest that the ACE I/D polymorphism could be a risk factor for patients with lung cancer.

Study: the lack of significant association of the catechol-O-methyl transferase (COMT) gene polymorphism in violent offenders with mental retardation.

Little is known about criminality of cognitively impaired people and also there have been no reports on the relationship between catechol-O-methyl transferase (COMT) and committed Mental Retardation (MR) subjects. In the present study, the association between committed (violent offences) MR subjects and genetic variants of COMT were investigated by using polymerase chain reaction and based restriction fragment length polymorphism methods. During 6 years of follow-up, 36 violent offenders with mild MR were investigated. Thirty-six control volunteers were included in the study as a control group. H/L polymorphism of the COMT gene was investigated in these two groups. In conclusion, the COMT gene genotype distribution and allele frequency is not significantly different between the two groups (p > 0.05). This result suggests that the H/L polymorphism of the COMT gene does not show an association with the potential of "commits-violent offense" of Turkish subjects with mental retardation, compared with control group.

The catechol-O-methyl transferase Val158Met polymorphism and susceptibility to cannabis dependence.

Cannabis stimulates dopamine release and activates dopaminergic reward neurons in central pathways that lead to enhanced dependence. Catechol-O-methyl transferase (COMT) inactivates amplified extraneuronally released dopamine. A functional polymorphism (COMT Val158Met) resulting in increased enzyme activity has been associated with polysubstance abuse and addiction to heroin and methamphetamine. The aim of this study was to examine the relationship between the COMT Val158Met polymorphism and use of cannabis. Fifty-five cannabis users and 75 normal controls were enrolled in this study. Polymerase chain reaction-based genotyping was used to evaluate the presence of COMT gene polymorphism. There was a difference in genotype frequencies between cannabis users and controls, including the distribution of the COMT genotypes (H/H, H/L) (P < 0.001) and alleles (H, L) (P < 0.01), when comparing the patient groups and the control individuals. However, LL genotype distribution was similar between the groups. These results suggest a significant association between COMT Val158Met polymorphism and susceptibility to cannabis dependence.

Association of angiotensin-converting enzyme gene insertion/deletion polymorphism with allergic contact dermatitis.

Angiotensin-converting enzyme (ACE) plays an important role in the physiological control of blood pressure and inflammation. Insertion/deletion (I/D) polymorphism of the gene for ACE was investigated in relation to cardiovascular, cerebrovascular, neurodegenerative and inflammatory diseases. The purpose of the present study was to investigate the possible association between allergic contact dermatitis and insertion/deletion polymorphism of the ACE gene. A total of 90 patients with allergic contact dermatitis and 160 control persons were enrolled in the present study. ACE I/D genotypes were determined by the polymerase chain reaction. Allelic frequencies and genotype distribution of the ACE I/D polymorphism in the patient group were significantly different from control group (ACE II genotype 30.0% versus 17.5%, P = 0.022; ACE I allele 51.7% versus 39.4%, P = 0.008). Our data suggest that the ACE polymorphism could be a risk factor for patients with allergic contact dermatitis.

Human arylamine N-acetyltransferase 2 polymorphism and susceptibility to allergic contact dermatitis.

BACKGROUND: N-acetyltransferase 2 (NAT2) polymorphism may be involved in the pathogenesis of allergic contact dermatitis. OBJECTIVE: The present study was designed to evaluate whether acetylation polymorphism plays a role in the susceptibility to p-Phenylenediamine (PPD) sensitization. METHODS: The frequencies of seven NAT2 point mutations, namely G191A, C282T, T341C, C481T, G590A, A803G, and G857A, and genotypes were determined by PCR/RFLP in a total of 70 patients with allergic contact dermatitis to PPD and 100 control subjects with no history of allergy, atopy, lung disease, diabetes mellitus and cancer. RESULTS: Genotypes coding rapid acetylation were detected in 52.9% and 37.0% of patients with contact dermatitis and control subjects, respectively (P = 0.04). The frequency of the NAT2*4 allele and NAT2*4/*4 genotype, coding for rapid acetylation, were also significantly higher in the contact dermatitis patients than in the control subjects (P = 0.003). CONCLUSION: Our results suggest an association between rapid acetylation polymorphism and susceptibility to PPD sensitization.

Rho kinase expression and its central role in ovine gallbladder contractions elicited by a variety of excitatory stimuli.

Rho kinase has contractile activity, which induces Ca2+ sensitization in various cells. Several receptors are linked to the Rho/Rho-kinase pathway. Therefore, in this study we aimed to demonstrate the central importance of this novel pathway for diverse excitatory stimuli in the smooth muscle of the sheep gallbladder. Accordingly, the effects of a Rho kinase inhibitor, (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate (Y-27632, 10(-8)-3 x 10(-5) M), were investigated on cholecystokinin-8 (CCK-8, 10(-8) M), endothelin-1 (10(-8) M), carbachol (10(-6)-10(-5) M), 5-hydroxytryptamine (5-HT, 10(-6)-10(-5) M), histamine (10(-6)-10(-5) M), phenylephrine (10(-5)-10(-4) M), neurokinin A (10(-7)-10(-6) M), electrical field stimulation (40 V, 0.5 ms, 2, 4, 8, 16, 32 Hz, 15 s, 3 min intervals) and potassium chloride (KCl, 25-50 mM)-induced contractions as well as spontaneous contractile activity. Electrical field stimulation evoked tetrodotoxin (3 x 10(-6) M)-sensitive reproducible contractions, which were inhibited by atropine (2 x 10(-6) M) and potentiated by eserine (5 x 10(-7) M). EFS-induced contraction was significantly inhibited by Y-27632 (10(-5) M). In addition, spontaneous contractile activity was suppressed in the presence of the compound (10(-6)-10(-5) M). This Rho kinase inhibitor also dramatically decreased the contractions elicited by 5-HT, neurokinin A and carbachol. KCl-induced contraction, which was not atropine-sensitive, was also conspicuously attenuated by Y-27632. Moreover, Y-27632 (10(-8)-3 x 10(-5) M) relaxed gallbladder strips that were contracted by histamine, endothelin-1, CCK-8 and phenylephrine in a concentration-dependent manner. pEC50 values for Y-27632 were 6.25+/-0.10, 5.79+/-0.12, 5.83+/-0.09 and 5.70+/-0.13 for the contraction elicited by histamine, CCK-8, endothelin-1 and phenylephrine, respectively. Furthermore, we also demonstrated Rho kinase protein expression (ROCK-1 and ROCK-2) by Western blot analysis. In conclusion, ROCK is expressed in the smooth muscle of the ovine gallbladder, and it has a central role in the contractile activity induced by diverse excitatory stimuli.

Influence of angiotensin-converting enzyme gene insertion/deletion polymorphism on rheumatic valve involvement, valve severity and subsequent valve calcification.

BACKGROUND AND AIM OF THE STUDY: The relationship between the severity of chronic rheumatic heart disease (RHD) and predisposing factors is unknown, and genetic predictors for severe scarring and calcification of the mitral valve are not well defined. A high angiotensin-converting enzyme (ACE) activity has been demonstrated in valve tissue. Thus, a case-control study was conducted to investigate any possible relationship between ACE gene polymorphisms and chronic mitral valve disease severity and calcification. METHODS: This case-control study included 82 patients (24 males, 58 females; mean age 40.3 +/- 14.7 years) with chronic rheumatic mitral valve, and 154 control subjects (53 males, 101 females; mean age 43.4 +/- 13.4 years). ACE gene insertion/deletion (I/D) polymorphisms were identified using polymerase chain reaction methods. RESULTS: Among RHD subjects, 31 (30.6%) were D/D, 25 (32.7%) were I/D, and 26 (18.8%) were I/I. Among controls, 57 (57.4%) were D/D, 69 (61.3%) were I/D, and 28 (35.2%) were I/I. The frequency of ACE I/I genotype was higher in RHD subjects than in controls (chi2 = 7.4, df = 2, p < 0.030; D/D versus I/D versus I/I), or (chi2 = 5.5, df = 1, p < 0.019; DD + ID versus II). Predisposition to RHD was significantly less frequent in the D/D genotype. There was no statistically significant difference in the genetic analysis of RHD with respect to mitral valve score, severity of mitral regurgitation and left atrial diameter. Mitral valve calcification was significantly associated with a higher frequency of I/I genotype and I/D genotype than D/D genotype alone (chi2 = 6.2, df = 2, p = 0.043). The ACE I/I genotype was associated with a predisposition to a greater risk of severe calcific valve disease. CONCLUSION: The ACE I/I genotype is more common in patients with rheumatic valve disease than in the normal population. This suggests that the ACE gene polymorphism may be involved in the pathogenesis of rheumatic heart disease.

Effects of caffeine on placental total nitrite concentration: A 21-day, vehicle-controlled study in rats.

BACKGROUND: Nitric oxide (NO) is a potent vasodilator that might have an10 important role in the modulation of maternal and fetal vascular tone during pregnancy. The effects of caffeine intake on maternal and fetal hemodynamic properties during pregnancy have been investigated in several human and animal studies. However, based on a literature search, there has been no study of placental total nitrite (a stable product of NO) concentration (PTNC) in pregnant humans or rats given caffeine. OBJECTIVE: The aim of this study was to assess the effects of caffeine intake 10 on PTNC in rats. METHODS: This 21-day, vehicle-controlled study was conducted at the Department10 of Pharmacology, Gaziantep University Hospital, Gaziantep, Turkey. Female Wistar rats were randomly assigned; based on age and weight, to receive 25, 50, or 100 mg/kg QD caffeine or 50 mg/kg QD isotonic saline solution (vehicle; age-matched control group), intraperitoneally for 21 days. After euthanization of the rats and cesarean section, the numbers of fetuses and fetal deaths were counted. The lengths and weights of the fetuses in each study group were noted. PTNC in the rats was determined using the Greiss reaction. RESULTS: This study included 26 rats (7, 7, and 6 rats in the groups receiving10 25, 50, and 100 mg/kg. d caffeine, respectively; 6 rats in the control group). The mean (SD) lengths of the fetuses of the rats given 25, 50, and 100 mg/kg · d caffeine (4.90 [0.15], 4.02 [0.27], and 3.45 [0.17] mm, respectively) were significantly less compared with controls (5.10 [0.18] mm) (all, P < 0.001), as were the mean (SD) weights of the fetuses of rats given caffeine (5.86 [0.24], 4.97 [0.59], and 3.41 [0.23] g, respectively) versus controls (6.18 [0.21] g) (all, P < 0.001). The mean (SD) PTNCs in rats given 25, 50, and 100 mg/kg. d caffeine (19.82 [1.97], 29.39 [2.07], and 45.51 [7.66] nmol/g, respectively) were significantly higher compared with controls (16.10 [2.12] nmol/g) (all, P < 0.001). CONCLUSIONS: The results of this study in rats suggest that caffeine intake 10 might increase NO production in the placenta. In addition, based on our findings and those from previous studies, we suggest that this increase might be an adaptive physiologic response to prevent undesirable effects of caffeine on vascular tone during pregnancy.

Angiotensin-converting enzyme insertion-deletion polymorphism in primary open-angle glaucoma.

PURPOSE: To investigate the hypothesis that primary open-angle glaucoma (POAG) is associated with a common insertion-deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene. METHODS: ACE I/D polymorphism was investigated in a control group of healthy subjects (n = 101) and in a group of patients diagnosed with POAG (n = 104). Polymerase chain reaction detection of I/D polymorphism was used to determine the presence of the two ACE alleles in the groups. RESULTS: Neither the I/D genotype distributions nor the allele frequencies differed significantly between POAG and control subjects (DD genotype 34.6 vs. 39.6%; ID genotype 53.9 vs. 40.6%; II genotype 11.5 vs. 19.8%, p = 0.1; D allele 61.5 vs. 60%; I allele 38.5 vs. 40%, p = 0.8). CONCLUSION: We could not identify a possible association of the I/D polymorphism in the ACE gene with POAG, however further studies with larger patient numbers in different populations are required to clarify the role of ACE gene in susceptibility to POAG.

Association between angiotensin converting enzyme gene polymorphism and coronary artery disease in individuals of the South-Eastern Anatolian population.

OBJECTIVE: The deletion (D) allele of the angiotensin-converting enzyme (ACE) gene has been proposed as a genetic marker of the risk of coronary artery disease (CAD). In this study we aimed to determine the relevance of ACE gene polymorphism for coronary artery disease in the South-Eastern Anatolian population. METHODS: Angiotensin converting enzyme genotypes were determined in 133 CAD patients who underwent coronary angiography. Severity of CAD was subgrouped according to the number of stenotic vessels on coronary angiography. The control group was selected from 154 healthy volunteers. Angiotensin converting enzyme genotypes were determined by agarose gel sizing after polymerase chain reaction (PCR) amplification. RESULTS: Frequency of ACE DD genotype did not differ between patients with CAD and control subjects. However the ACE II genotype in CAD group was significantly less frequent than in control group (p=0.02). The relative risks were 0.9 (95% CI=0.56-1.43) for the DD genotypes, and 2.2 (95% CI=1.09 - 4.11) for the II genotype. In the 2-vessel CAD subgroups, the II genotypes were significantly different from control group. CONCLUSION: Our study did not confirm the possibility that the ACE DD genotypes may be associated with predisposition to CAD in this certain population but there is a relationship between the least frequencies of the II genotype and CAD. The II genotype seems to be an independent protective factor for CAD in the South-Eastern Anatolian population.