Analysis of association between histamine receptor gene HRH1, HRH2, HRH3, HRH4 polymorphisms and asthma in children

Asthma is a common multifactorial disease characterized by chronic inflammation of the respiratory tract. Insufficient control of asthma symptoms significantly reduces the patient’s quality of life, leads to the risk for more severe disease and disability. It is important to research the role of gene polymorphisms encoding proteins involved in various stages of histamine metabolism, which is one of the known mediators of allergic reactions.The aim of the study was to investigate histamine receptor gene polymorphisms (HRH1, HRH2, HRH3, HRH4) in children with asthma and the control group.Methods. The study of HRH1 (rs901865), HRH2 (rs2067474), HRH3 (rs3787429), HRH4 (rs11665084) gene polymorphisms in asthma patients and healthy individuals aged 2 - 17 years of different ethnicities living in the Republic of Bashkortostan was carried out. Genotyping of polymorphisms was performed by polymerase chain reaction with fluorescence detection.Results. In Tatars, rs901865*CT genotype and rs901865*T allele of HRH1 gene were associated with asthma development and decrease in spirometry measures (MEF25). In Tatars, a statistically significant model of the interaction between HRH1 (rs901865), HRH3 (rs3787429), and HRH4 (rs11665084) gene polymorphisms that leads to the risk of asthma was established.Conclusion. The results of this study reveal certain aspects of asthma pathogenesis and suggest the possible involvement of polymorphic variants of histamine receptors genes HRH1, HRH3, HRH4 in the development of asthma.

Initial Study on COMT and DRD2 Gene Polymorphisms as Well as the Influence of Temperament and Character Trait on the Severity of Alcohol Craving in Alcohol-Dependent Patients

The main aim of this work was to determine the impact of COMT and DRD2 gene polymorphisms together with temperament and character traits on alcohol craving severity alcohol-dependent persons. The sample comprised of 89 men and 16 women (aged 38±7). For the sake of psychological assessment various analytic methods have been applied like the Short Alcohol Dependence Data Questionnaire (SADD), Penn Alcohol Craving Scale (PACS) or Temperament and Character Inventory (TCI) test. The SNP polymorphism of the analyzed genes was determined by Real Time PCR test. The results showed, that the COMT polymorphismmay have an indirected relationship with the intensity and changes in alcohol craving during abstinence. The DRD2 receptor gene polymorphisms are related with the intensity of alcohol craving. It seems that the character traits like “self-targeting”, including “self-acceptance”, are more closely related to the severity of alcohol craving and polymorphic changes in the DRD2 receptor than temperamental traits. Although this is a pilot study the obtained results appeared to be promising and clearly indicate the link betweengene polymorphisms alcohol craving and its severity.

NR3C1 Glucocorticoid Receptor Gene Polymorphisms Are Associated with Membranous and IgA Nephropathies

Glomerular diseases (GNs) are responsible for approximately 20% of chronic kidney diseases. Glucocorticoid receptor gene (NR3C1) single nucleotide polymorphisms (SNPs) are implicated in differences in predisposition to autoimmunity and steroid sensitivity. The aim of this study was to evaluate the frequency of the NR3C1 SNPs—rs6198, rs41423247 and rs17209237—in 72 IgA nephropathy (IgAN) and 38 membranous nephropathy (MN) patients compared to 175 healthy controls and to correlate the effectiveness of treatment in IgAN and MN groups defined as a reduction of proteinuria <1 g/24 h after 12 months of treatment. Real-time polymerase chain reactions and SNP array-based typing were used. We found significant rs41423247 association with MN (p = 0.026); a significant association of rs17209237 with eGFR reduction after follow-up period in all patients with GNs (p = 0.021) and with the degree of proteinuria after 1 year of therapy in all patients with a glomerulopathy (p = 0.013) and IgAN (p = 0.021); and in the same groups treated with steroids (p = 0.021; p = 0.012). We also observed the association between rs41423247 and IgAN histopathologic findings (p = 0.012). In conclusion, our results indicate that NR3C1 polymorphisms may influence treatment susceptibility and clinical outcome in IgAN and MN.

Follicle-stimulating hormone (FSH) receptor gene polymorphisms in Iraqi patients with non-obstructive azoospermia

Background: Follicle-stimulating hormone (FSH) is a pivotal hormone for male fertility, and its action on gonads is exerted by FSH receptors (FSHRs). Objectives: To examine whether the presence of FSHR gene single nucleotide polymorphisms (SNPs), G919A and A2039G, involved in non-obstructive azoospermia (NOA) in Iraqi infertile men. Methods: Two common SNPs, A919G and A2039G, in the FSHR gene were analyzed in 104 subjects (70 infertile patients with NOO: 33 NOA patients were not receiving treatment and 37 were on infertility treatment, and 34 normozoospermic fertile men as controls). Results: The results revealed that the homozygous wild genotype (AA) of rs6165 FSHR gene SNP was more abundant than (AG) and (GG) genotypes in both groups of infertile NOA patients with a frequency of 49% in those who untreated, 81% in patients undergoing treatment and in the control group 41%. Whereas, the highest percentage of heterozygous genotype (AG) in the fertile control group was 41% when compared to NOApatients with a genotype frequency of 24% (for those who untreated) and 11% (for patients on treatment), respectively; with (A) allele frequency of 86% and the observed frequency of (G) allele was only 14% in the patients’ group as compared to that of controls that were (65 %) and (35 %), respectively. The rs6166 genotyping revealed that the homozygous wild genotype (GG) of FSHR gene was more abundant than (AG) and (AA) genotypes in NOA patients receiving infertility treatment with a frequency of (68%), in NOA patients who didn’t receive treatment 49%, while the lowest frequency was detected in the healthy fertile control group (47%). Conclusions: These results support the evidence that rs6165 and rs6166, FSHR SNPs, might be involved in the pathogenesis and protection against NOA, respectively.