Sublingual buprenorphine/naloxone treatment is not affected by OPRM1 A118G and BDNF Va66Met polymorphisms, but alters the plasma beta-endorphin and BDNF levels in individuals with opioid use disorder

The study aimed to examine the genetic contribution to buprenorphine (BUP) treatment in individuals with opioid use disorder (OUD), with a specific focus on BDNF and OPRM1 genes. A total of 113 controls and 111 OUD patients receiving sublingual BUP/naloxone were enrolled. OPRM1 A118G and BDNF Val66Met polymorphisms were investigated by PCR-FRLP. Plasma BDNF and beta-endorphin levels were assessed by ELISA kits in both groups. Blood BUP levels were measured by LC-MS/MS and normalized with daily BUP dose (BUP/D). OPRM1 A118G and BDNF Val66Met polymorphisms didn't have an effect on plasma beta-endorphin and BDNF levels in OUD patients, respectively. Interestingly, OUD patients had significantly higher plasma BDNF and lower beta-endorphin levels compared to the controls (p < 0.001). A negative and significant correlation between plasma BUP/D and BDNF levels was found. Age onset of first use was associated with OPRM1 A118G polymorphism. The findings indicated that sublingual BUP/naloxone may increase plasma BDNF levels, but may decrease beta-endorphin levels in individuals with OUD. Plasma BDNF level seemed to be decreased in a BUP/D concentration-dependent manner. © 2022 Elsevier B.V

Optimization of PCR-RFLP method for genotyping of GHSR rs2232165 Gene Polymorphism and Determination of allele frequency in Turkish men

Çağımızın ciddi sorunlardan biri olan alkol bağımlılığı, genetik, çevresel, kültürel, gelişimsel ve nörobiyolojik faktörlerin etkisiyle ortaya çıkmaktadır. Son yıllarda yeme davranışı nörobiyolojisi ile bağımlılık yapan maddelere aşerme davranışının nörobiyolojisinin benzer özelliklere sahip olduğunun keşfedilmesi araştırmacıları, alkol bağımlılığı ile grelin gibi besin alımında önemli olan hormonlar arasındaki ilişkiyi araştırmaya sevk etmiştir. Alkol kullanım bozukluğunda ve alkole aşermede grelin sisteminin önemi mevcut çalışmalar tarafından ortaya konulmasına karşın bu ilişkinin biyolojik mekanizmasının aydınlatılması için daha çok çalışmaya ihtiyaç vardır. Bu nedenle, bu çalışmada, alkol kullanım sorunu olan Türk erkeklerinde, grelin reseptörünü kodlayan GHSR genindeki rs2232165 polimorfizminin alkol kullanım sorunu ile ilişkisi araştırılmıştır. Çalışmaya alkol kullanım bozukluğu tanısı konmuş 72 erkek birey ile herhangi bir madde bağımlılığı olmayan 82 sağlıklı erkek dahil edilmiştir. GHSR rs2232165 gen polimorfizmi, ilk defa bu çalışmada optimize edilen PCR-RFLP yöntemi ile genotiplendirilmiştir. GHSR rs2232165 polimorfizmi için alel frekansları alkol kullanım sorunu olan grupta (n:144); C aleli için 0,99 (n:142), T aleli için 0,01 (n:2) olarak hesaplanmıştır. Karşılaştırma grubunda ise (n:164), C aleli frekansı 0,98 (n:161), T aleli frekansı 0,02 (n:3) olarak belirlenmiştir. İki grup arasında, T alel frekansı açısından istatistiksel olarak anlamlı bir fark bulunmamıştır (p>0,05). Gen polimorfizmleri, çevresel faktörlerden etkilenmediği için Türk erkeklerindeki minör alel frekansını (MAF) belirlemek için iki gruptaki bireyler birleştirilmiş (n=154) ve Türk erkeklerinde GHSR rs2232165 polimorfizminin MAF değeri 0,02 olarak belirlenmiştir. Bu çalışmada, çağımızda alkol kullanım bozukluğu kadar önemli olan obezite etiyolojisinde de rol oynayan GHSR rs2232165 polimorfizminin Türk erkeklerinde alel frekansı ile ilgili ilk veriler toplanmıştır.Alcohol addiction, which is one of the crucial problems of the current era, arises with the effects of genetic, environmental, culturel, developmental and neurobiological factors. In recent years, the discovery that the neurobiology of eating behavior and the neurobiology of craving for addictive substances have similar characteristics has prompted researchers to investigate the relationship between alcohol addiction and hormones important in food intake such as ghrelin. Even though the importance of the ghrelin system in alcohol use disorder and alcohol craving has been stated by existing studies , more studies are needed to enlighten the biological mechanism of this relationship. Therefore, in this study the relationship between rs2232165 polymorphism in GHSR gene encoding ghrelin receptor and alcohol use disorder in Turkish men with alcohol use problem. Seventy-two individuals diagnosed with alcohol use disorder and 82 healthy men without any substance addiction were included in this study. The GHSR rs2232165 gene polymorphism was genotyped by PCR-RFLP which was optimized for the first time in this study. The allele frequency of the GHSR rs2232165 gene polymorphism was determined in the group with alcohol use problem (n:144) as 0,99 (n:142) for C allele and 0,01 (n:2) for T allele. The frequency of the C allele was 0,98 (n:161) and T allele was 0,02 (n:3) in the healthy group. There was no statistically significant difference between two groups in terms of T allele frequency. Since gene polymorphisms are not affected by environmental factors, individuals in two groups were combined (n=154) in order to determine minor allele frequency (MAF) in Turkish males, and the MAF value of GHSR rs2232165 polymorphism in Turkish males was determined as 0,02. In this study, the first data on the allele frequency of GHSR rs2232165 polymorphism, which plays a role in the etiology of obesity, which is as important as alcohol use disorder in the current era, were collected in Turkish males

The involvement of miRNAs in CYP450 gene expression: A brief review of the literature

Drug biotransformation is a critical process in metabolic elimination of drugs. It occurs mainly in the liver as well as in other tissues such as kidney and small intestine and consists of three stages: Phase I, Phase II and Phase III. Drugs are converted to a more polar and hydrophilic metabolites during Phase I and Phase II, which are excreted by a variety of membrane transporters such as P-glycoprotein and Multidrug Resistance Protein 1 in Phase III. Cytochrome P450 enzyme isoforms achieve 80% of Phase I metabolism. It is well described that there is inter-individual drug response variability such as adverse drug reactions or reduced drug efficacy and that genetic variation within the sequence of biotransformation-related genes affects these different therapeutic outcomes observed between individuals. However, genetic factors cannot completely explain inter-individual differences. Recent studies have shown that epigenetic factors such as histone modification, DNA methylation and non-coding miRNAs heavily influence drug biotransformation through post-transcriptional regulation of metabolism gene expression. It is important to understand the causes of alterations in drug metabolism since varied biotransformation may lead to adverse drug effects or a loss of efficacy. Therefore, in this review, the effects of miRNAs in CYP450 gene expression will be discussed briefly in the light of recent studies

Validation and Optimization of an Analytical Method Based on Cold Vapor Atomic Absorption Spectrometry for the Determination of Mercury in Maternal Blood, Cord Blood, and Placenta Samples

Yuksel, Bayram/0000-0001-7686-8648; Kaya-Akyuzlu, Dilek/0000-0002-3305-0587WOS: 000410870100006In this study, a simple and sensitive cold vapor atomic absorption spectrometry (CVAAS) method was developed and validated for the determination of mercury in maternal blood, cord blood, and placenta samples. Biological samples were obtained from 113 mother -newborn pairs. Infant characteristics such as birth weight, birth length, and head circumference were recorded. Microwave-assisted acid digestion was applied and a cold vapor module was utilized for atomization. The method showed linearity in the range of 0-20 pg/L with a detection and quantification limit equal to 0.231.1g/L and 0.76 pg/L, respectively, as well as very good repeatability not exceeding 3%. The calibration curve was characterized by a high correlation coefficient (r2=0.9992). Validation was performed in terms of precision and accuracy with the use of certified reference materials (CRM). The method was applied to the analysis of spiked CRM samples yielding satisfactory results (97.4-101.2%). The mean mercury levels of maternal blood, placentas, and cord blood were 3.23 1.46 pg/L, 12.24 11.50 g/kg, 3.69 3.44 pg/L, respectively. As a result of the statistical analysis, a significant correlation was found between placenta-Hg and cord blood-Hg levels (r=+0.231, p=0.014). In addition, birth head circumference and cord blood -Hg levels were found to be correlated to each other (r=+0.318, p=0.033).Ankara University Scientific Research Projects Coordination Unit (BAP)Ankara University [15B0217001]This study was financially supported by the Ankara University Scientific Research Projects Coordination Unit (BAP). Project Number: 15B0217001

Effect of PDYN rs2281285, rs2235749 and rs910080 gene polymorphisms on the intensity of depression symptoms and negative craving in heroin addicts

The present study was undertaken to explore whether prodynorphin (PDYN) polymorphisms have an effect on the intensity of depressive symptoms and negative craving in heroin addicts in a sample of 100 heroin addicts and 108 controls. PDYN rs2281285, rs2225749 and rs910080 polymorphisms were analyzed by PCR-RFLP. Craving and the intensity of depressive symptoms were measured by the Substance Craving Scale and the Beck Depression Inventory-II, respectively. A significant association between depression severity and PDYN rs2281285 (P=0.026) and rs2225749 (P=0.038) polymorphisms was detected. PDYN rs2225749 variation showed a trend association with increased negative craving (P=0.066). We also examined the associations between heroin dependence and PDYN rs2281285, rs2225749 and rs910080 gene polymorphisms at the gene and haplotype levels. The AAA haplotype was more frequent in heroin addicts and shown to be significantly associated with increased risk for heroin dependence (OR, 8.922; 95% CI, 1.116-71.313; P[removed