scholarly journals Study of the polymorphic variants of the PIP5K2A gene association with the comorbidity of alcoholism and affective disorders

Author(s):  
E. V. Mikhalitskaya ◽  
O. V. Roshchina ◽  
S. A. Ivanova ◽  
N. A. Bokhan

One of the common pathogenetic mechanisms of the formation of alcohol dependence and depressive disorders can be a violation of the neurotransmitter systems, in particular — dopamine. Phosphatidylinositol-4-phosphate-5-kinase type 2 alpha (PIP5K2A) plays an important role in the regulation of neuronal excitability and synaptic dopamine neurotransmission. The aim of this study was to assess the presence of associations of the PIP5K2A gene polymorphic variants with the comorbid course of alcohol dependence and depressive disorders. This study showed differences in the frequency of the genotype distribution of 3 PIP5K2A gene polymorphisms (rs946961, rs1132816, and rs1417374) both between patient groups compared with the control group, and between the patient group and the group with the comorbid course of disorders.

1970 ◽  
Vol 21 ◽  
pp. 325-329
Author(s):  
Ya. M. Mishchuk ◽  
Ye. V. Kharkivska ◽  
S. V. Serha ◽  
S. Ye. Shkliar ◽  
V. B. Katrii ◽  
...  

Aim. To estimate the frequency of XRCC1 codon 399 polymorphic variants in bladder cancer patients and in a control group and define association of this polymorphism with a bladder cancer in Ukrainian patients. Methods. We determined the allele frequencies for 111 patients and 92 controls. Genotyping was performed by PCR-RELP method. Results. The distribution of genotypes in control group was: Arg/Arg – 48 % (n=44), Arg/Gln – 41.3 % (n=38), Gln/Gln – 10.7 % (n=10), whereas in group of patients with a bladder cancer the following distribution was observed: Arg/Arg – 56.8 % (n=63), Arg/Gln – 27.9 % (n=31), Gln/Gln – 15.3 % (n=17). Genotype distribution in control group was within Hardy-Weinberg equilibrium (χ2=59.7, p<0.0001), whereas in patient group it was not (χ2=0.172, p=0.678). No significant association was observed between the XRCC1 Arg399Gln polymorphism and bladder cancer risk. Conclusions. It is indicated that XRCC1 codon 399 polymorphism may not contribute to bladder cancer susceptibility in the Ukrainian population. Keywords: bladder cancer, polymorphism, XRCC1 gene, the cancer risk.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Y.Y. Voitiv

Purpose - to analyze the frequency of polymorphic variants of tissue inhibitors ofmetalloproteinase-2 (G303 → A) gene in patients with intestinal anastomotic leak.Material and methods. The object of the study comprises 61 patients with anastomotic leakand connective tissue pathology, who were treated in the department of thoracoabdominalsurgery of Shalimov National Institute of Surgery and Transplantology during 2017-2020. Laboratory, genetic, histological studies and statistical analysis were performed.Results. As a result of genetic and statistical analysis of the tissue inhibitors ofmetalloproteinase-2 (G303 → A) gene polymorphisms, genotype variants have beenidentified that are associated with the risk of anastomotic leak in the hollow digestiveorgans. Significant differences in the distribution of genotypes in the studied groupswere revealed. Analysis of the multiplicative model of inheritance of tissue inhibitors ofmetalloproteinase-2 (G303 → A) gene showed compliance of genotype distribution withHardy-Weinberg's law. All models of inheritance were analyzed and the best model withthe lowest Akaike Information Criterion, which turned out to be a recessive model, hasbeen determined.Conclusions. It is statistically significant that in the group of patients with intestinalanastomotic leak the GG variant of the TIMP-2 gene was detected in 1,6 times moreoften. Carriers of minor homozygotes of AA genotype in the group with suture failurewere not detected, while a similar genotype in the control group was found in 10%(p <0,05).


Author(s):  
Т.М. Рожнова ◽  
В.А. Спицын ◽  
С.В. Макаров ◽  
С.В. Костюк

Аддиктивные расстройства относятся к мультифакториальным заболеваниям с клинической, генетической и нейрофизиологической гетерогенностью и высокой коморбидностью с другими расстройствами психического спектра. Определяющее влияние на фенотипическую дисперсию расстройств поведения зависимого характера принадлежит генотипу. Полиморфные варианты генов нейромедиаторных систем головного мозга, кодирующих белки, участвующие в регуляции эффекторных реакций и метаболизме психоактивных веществ (ПАВ), можно рассматривать как маркёры поведенческих паттернов и индивидуальной предрасположенности к зависимому поведению. Цель исследования - анализ полиморфных вариантов генов DRD2/ANKK1 и SLC6A3 дофаминергической системы головного мозга у больных алкоголизмом. Генотипирование по TaqIA-полиморфизму в локусе ANKK1/DRD2 (rs1800497) и VNTR-полиморфизму в гене SLC6A3 (DAT1) проводили с использованием метода ПЦР. Выявлено статистически достоверное преобладание частоты аллеля ANKK1*A1 и генотипа ANKK1*A1A2 в группе мужчин с наличием аддиктивного расстройства в форме алкогольной зависимости по сравнению с фенотипически здоровыми представителями контрольной группы (p<0,001). Частота аллеля *А2 и генотипа *A2A2 в исследуемой группе статически значимо ниже этого показателя контрольной выборки. Аллель ANKK1*A1 является фактором риска развития алкогольной зависимости (RR=4,69; EF=0,15) с теснотой связи средней степени (j=0,21), а ANKK1*A2 обладает протекторным свойством (RR=0,84; PF=0,79). Полученные данные указывают на возможность использования генотипирования генов дофаминэргической системы головного мозга для оценки индивидуальной предрасположенности к алкогольной зависимости - у носителей *A1 гена DRD2/ANKK1 риск формирования зависимости в 4,69 раза выше гомозигот по варианту *А2. Addictive disorders are multifactorial diseases with clinical, genetic and neurophysiological heterogeneity and high comorbidity with other disorders of the mental spectrum. The decisive influence on the phenotypic dispersion of disorders of behavior of a dependent nature belongs to the genotype. Polymorphic variants of genes of the neurotransmitter systems of the brain that encode proteins involved in the regulation of effector reactions and the metabolism of psychoactive substances can be considered as markers of behavioral patterns and an individual predisposition to dependent behavior. Genotyping by TaqIA polymorphism at the ANKK1/DRD2 locus (rs1800497) and VNTR polymorphism in the SLC6A3 gene (DAT1) was performed using the PCR. A statistically significant predominance of the frequency of the ANKK1*A1 allele and the ANKK1*A1A2 genotype was revealed in the group of men with the presence of addictive disorder in the form of alcohol dependence compared to phenotypically healthy representatives of the control group (p <0.001). The frequency of *A2 and genotype *A2A2 were statistically significantly lower in the study group than in the control. The ANKK1*A1 allele is a risk factor for the development of alcohol dependence (RR=4.69; EF=0.15) with a moderate linkage (j=0.21), and ANKK1*A2 has a protective property (RR=0.84; PF=0.79). The data obtained indicate the possibility of using genotyping of the genes of the dopaminergic system of the brain to assess an individual predisposition to alcohol dependence - in carriers of *A1 of the DRD2/ANKK1 gene, the risk of dependence formation is 4.69 higher than homozygotes in the *A2 variant.


Author(s):  
A. E. Nikolishin ◽  
V. M. Brodyansky ◽  
N. A. Chuprova ◽  
A. V. Solovieva ◽  
A. O Kibitov

Aim. Test the hypothesis about the effect of polymorphisms of the DA system on the risk of developing depression in patients with alcohol dependence. Material and methods. 104 patients: 64 patients with a combination of diagnoses of “alcohol dependence” and “depression” (F10.2 and F32, F33 according to ICD-10, average age 41.23 ± 9.903 years) and 40 patients with a diagnosis of alcohol dependence (F10 .2 according to ICD-10, average age 45.57 ± 10.853 years) and 113 control (average age 43.65 ± 4.318 years). Results. In patients with a combination of AD and depression, the frequency of occurrence of the C allele C polymorphism rs1611115 of the DBH gene is higher than in the control group (p = 0.087, trend). In patients with a combination of AD and depression, the frequency of occurrence of the A allele of the rs1108580 polymorphism of the DBH gene is higher than in patients with AD (p = 0.059, trend). In patients with AD allele A, the DBH gene rs1108580 polymorphism increases the risk of depression by 174.0% (p = 0.009), the DBH gene rs1108580 AA polymorphism increases the risk of depression by 684.1% (p = 0.010), the rs1108580 gene AG polymorphism rs1108580 in the gene DBH increases the risk of depression by 261.1% (p = 0.010). Conclusion. It has been shown for the first time that polymorphic variants of the rs1108580 locus of the DBH gene act as important risk factors for depression in patients with AD. Polymorphism rs1611115 of the DBH gene can also play an important role in the development of depression in patients with AD, which requires further study.


2021 ◽  
Vol 2 (04) ◽  
pp. 203-217
Author(s):  
Mustafa Al-Taie ◽  
Rayah Baban ◽  
Mouayed Hamed

Background: The most chronic disease prevalence in the Iraqi population are type-2 diabetes mellitus (T2DM) and hypertension (HT). One of the important causes of these chronic diseases is obesity. Resistin (RETN) is a major link between obesity and insulin resistance (IR) or T2DM (which induces IR). The action of RETN on IR is mediated by Toll-like receptor-4 (TLR4). TLR4 is a putative RETN receptor that has been suggested to participate in RETN-inducing inflammation and IR. Objectives: To study the association between serum RETN/TLR4 and IR in hypertensive patients with or without T2DM subjects. Methods: This cross-sectional study was conducted on 120 men that classified into four different groups. These groups consist of the following: 30 apparently control group, 30 patients with hypertension, 30 patients with T2DM but without HT and 30 hypertensive patients with T2DM. For all the subjects, serum RETN, TLR4 and serum insulin was estimated by using the ELISA technique. Results: Our results showed that mean levels of the serum RETN and TLR4 were significantly elevated in all patient groups when compared with the control group. Also, a positive correlation between serum RETN and TLR4 was found in hypertensive patients with T2DM patients. Conclusions: Serum RETN and TLR4 were higher in all patient groups when compared with the control group. In addition, a positive correlation between RETN and IR in all study groups was noted. Then, we suggested a close association between RETN and TLR4 and their positive correlations with IR.


2020 ◽  
Author(s):  
Salehe Rezapour ◽  
Shiva Ahdi Khosroshahi ◽  
Hadi Farajnia ◽  
Fatemeh Mohseni ◽  
Manouchehr Khoshbaten ◽  
...  

Abstract Objective Uncoupling protein 2 (UCP2) is a regulator of insulin secretion, free fatty acid (FFA) concentrations and lipid metabolism that plays crucial roles in energy homeostasis. Last decade reports have described close association between UCP2 polymorphisms and nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus type 2 (T2DM). Results A higher prevalence of insertion/insertion genotype has been observed in T2DM patients compared with the control group (p value˂ 0.05). But, there was no difference in genotype distribution between NAFLD patients and control groups (p value > 0.05). NAFLD patients with D/D, D/I genotype had higher triglyceride, ALT and AST levels, and lower HDL level than healthy controls. Patients with T2DM together with D/D or D/I genotype also had significantly higher fasting serum glucose (FSG) level. While we found association between the 45 bp I/D polymorphism in 3ʹUTR of UCP2 and T2DM, existence of correlation between this polymorphism and NAFLD was not identified.


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Magda Shukry Mohammed ◽  
Rania Sayed Abd Elbaky ◽  
Hanan Mahmoud Ali ◽  
Tahani Abdelsalam Naguib

Abstract Background Omentin-1 a new anti-inflammatory adipokine has been identified as a major visceral (omental) secretory adipokine which plays important roles in glucose homeostasis, lipid metabolism, insulin resistance and diabetes. Objectives This study aimed to investigate the level of Omentin-1 in chronic kidney disease patients with and without type 2 diabetes mellitus. Methods The study included 70 patients who further subdivided into three subgroups (20 T2DM, 25T2DM+CKD, 25CKD) and 20 healthy subjects formed the control group. They subjected to full clinical examination, weight, height, waist and hip circumference and BMI was calculated.Lipid profile, omentin-1, kidney function test, UACR, and HbA1c were measured. Results Serum omentin-1 level was lower in all patient groups compared to healthy control. It’s level was lower in groups with T2DM than CKD only group. It had a negative correlation with HbA1c, cholesterol total, TGs, LDL-c and e-GFR, and a positive correlation with s.creatinine, UACR, BUN, HDL-c. The best cut off point of serum omentin-1 was  &lt; =330 ng/ml to differentiate group 3(T2DM+CKD) from control group using ROC curve analysis. Conclusion The results of the present study suggest that diabetes mellitus may be associated with lower omentin levels in CKD population .


2012 ◽  
Vol 32 (2) ◽  
pp. 93-99 ◽  
Author(s):  
Ines Cilenšek ◽  
Sara Mankoč ◽  
Mojca Globočnik Petrovič ◽  
Daniel Petrovič

Aim: Substantial data indicate that oxidative stress is involved in the development of diabetic retinopathy (DR). The aim of the present study was to investigate whether the genetic polymorphisms: polymorphic deletions of glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) and Ile105Val of the GSTP1 are associated with DR in Slovenian patients with type 2 diabetes.Methods: In this cross sectional case-control study 604 unrelated Slovene subjects (Caucasians) with type 2 diabetes mellitus were enrolled: 284 patients with DR (cases) and the control group of 320 subjects with type 2 diabetes of more than 10 years’ duration who had no clinical signs of DR. Genotypes were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP).Results: In our study, the deletion of the GSTM1 was found less frequent in cases with DR than in the controls (27.5% versus 44.4%;P< 0.001), whereas the deletion of GSTT1 was found significantly more often in cases than in the controls (49.3% versus 29.7%;P< 0.001). We did not find statistically significant differences in the genotype distribution in GSTP1 (Ile105Val) polymorphism between cases and controls (40.5% versus 46.0%).Conclusions: We may conclude that individuals homozygous for the deletion of GSTT1 are at an ≈ 2-fold-greater risk of DR, whereas the GSTM1 deficiency is associated with lower frequency of DR in type 2 diabetics.


Author(s):  
A. A. Streltsova ◽  
A. Ya. Gudkova ◽  
S. A. Pyko ◽  
E. N. Semernin ◽  
A. A. Kostareva

The objective of this study was to determine the association of polymorphic variants rs2305619 and rs3816527 of the PTX3 gene with clinical profile and outcomes in hypertrophic cardiomyopathy (HCM) patients.Methods and materials. The study population consisted of 153 patients ≥18 years old with a confirmed diagnosis of HCM. The control group included 200 healthy donors. Duration of follow-up was 11 years (2008–2019 yrs.). The study design included a new model for determining variants of the clinical profile and outcomes of HCM. Polymorphic variants rs2305619 and rs3816527 of the PTX3 gene were genotyped by polymerase chain reaction.Results. The mortality rate in patients ≥18 years old with 1, 2 and 3 adverse pathways of HCM progression was significantly higher, compared with those without adverse pathways (р<0.001). A combination of chronic heart failure (CHF) with midrange and reduced LVEF (<49 %) with 1, 2 and 3 adverse pathways in HCM patients occurred more frequently, compared with those who had CHF with preserved LVEF (≥50 %) (odds ratio (OR) = 0.168, 95 % confidence interval (CI) =0.068–0.412, р<0.001). The genetic testing showed no significant differences in genotype and allele frequencies of polymorphic variants rs2305619 and rs3816527 of the PTX3 gene in patients with HCM and control groups. It was found a tendency for increase in GG genotype frequency (p<0.068) and significant increase in G allele frequency of rs2305619 of the PTX3 gene in HCM patients ≥18 years old and CHF with mid-range and reduced LVEF (<49 %) (A:G, OR=0.521, 95 % CI=0.301–0.902, p<0.019). HCM patients (age – 63 [58; 75] years) and type 2 diabetes mellitus demonstrated high prevalence in AG and GG genotypes (p<0.008) and G allele frequencies of rs2305619 of the PTX3 gene (A:G, OR =1.952, 95 % CI=1.076–3.542, p<0.026).Conclusions. HCM progression along 1 and more adverse pathways in patients ≥18 years old has been characterized with adverse outcome. G allele of rs2305619 of the PTX3 gene is associated with CHF with mid-range and reduced LVEF (<49 %) in HCM patients ≥18 years old. The associations of G allele and AG and GG genotypes of rs2305619 of the PTX3 gene with diabetes type 2 are observed in elderly HCM patients.


2020 ◽  
Vol 22 (6) ◽  
pp. 568-576
Author(s):  
Marat Z. Saidov ◽  
Suleiman N. Mammaev ◽  
Halina M. Magadova ◽  
Rita Maratovna Balamirzoeva ◽  
Zulfia Sh. Magomedova ◽  
...  

BACKGROUND: Type 2 diabetes and arterial hypertension are frequent comorbidities under which activation the renin-angiotensin-aldosterone system is important pathogenetic link. The functional state of the RAAS is genetically determined. Genetic polymorphisms of the RAAS system associated with the development of both type 2 diabetes and arterial hypertension have been identified and mapped. Associations of polymorphic variants of the RAAS genes with type 2 diabetes and arterial hypertension among the inhabitants of Dagestan have not been studied. AIM: Studying the association of the most relevant polymorphic variants of the C521T and T704C AGT gene, as well as the A1166C AGTR1 gene with type 2 diabetes and when combining type 2 diabetes with arterial hypertension among Dagestan inhabitants. METHODS: We examined 16 patients with type 2 diabetes, 59 patients with type 2 diabetes combined with arterial hypertension and 51 patients with arterial hypertension, all residents of Dagestan. The control group included 47 healthy persons of the same age group. SNP polymorphisms were investigated by the method of allele-specific Real-Time PCR. The C521T and T704C polymorphisms of the AGT gene and the A1166C polymorphism of the AGTR1 gene were studied. RESULTS: In the group of patients with a combination type 2 diabetes with arterial hypertension, the genotype CT of the C521T polymorphism of the AGT gene is less common compared to the control (23% vs. 43%, 2 = 3,868, p = 0,049), OR score 0,4 (0,2-0,9 ). The situation is similar with the TC genotype of the T704C polymorphism of the AGT gene (39% versus 61%, 2 = 4,282, p = 0,039). OR was 0,4 (0,20,8).On the contrary, in the same patients, but the carriers of the homozygous CC genotype of the T704C polymorphism of the AGT gene, OR exceeded one and made 2.5 (1.02-5.9), the frequency of occurrence was 42% vs. 23%, 2 = 3,363, p = 0,05. The frequency of the mutant allele C of the A1166C polymorphism of the AGTR1 gene in patients with arterial hypertension alone was 31% vs. 14%, 2 = 5.496, p = 0,019, OR 2,5 (1,2-5,0). The frequency of the wild allele A in these same patients was 69% versus 84%, 2 = 5,496, p = 0,019, OR 0,4 (0,2-0,8). A similar situation is determined with the AA genotype (52% versus 73%, 2 = 3,609, p = 0,05), OR = 0,4 (0,1-0,9). CONCLUSIONS: The association of the C521T and T704C polymorphisms, as well as the A1166C candidate genes AGT and AGTR1 with type 2 diabetes and arterial hypertension, is an important component in assessing the susceptibility to the development of these diseases in Dagestan residents.


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