Receptor Gene Variants Research Articles

The CB1R rs2023239 receptor gene variant significantly affects the reinforcing effects of nicotine, but not cue reactivity, in human smokers.

IntroductionThe cannabinoid CB1 receptor (CB1R) has been shown in preclinical studies to be involved in nicotine reinforcement and relapse‐like behavior. The common single nucleotide polymorphism (SNP) rs2023239 may code for an alternative CB1R protein, alter CB1R expression, and be involved in nicotine dependence. To date, no study has explored the relationship between this SNP in CB1R and specific phenotypes of nicotine dependence.MethodsThe current study investigated the influence of CB1R rs2023239 in nicotine reinforcement and craving in regular cigarette smokers. Current smokers (n = 104, cigarettes per day ≥ 10) were genetically grouped (C allele group vs. No C allele group) and underwent laboratory measures of nicotine reinforcement and smoking cue‐elicited craving. Nicotine reinforcement was assessed using a forced choice paradigm, while a cue‐reactivity procedure measured cue‐elicited craving.ResultsThese results show that smokers with the C allele variant (CC + CT genotypes) experienced a lower nicotine reinforcement effect compared to those without the C allele (TT genotype). These results were similar in both our subjective and behavioral reinforcement measures, though the subjective effects did not withstand controlling for race. There was no difference between genotype groups with respect to cue‐elicited craving, suggesting a lack of influence in cue reactivity.ConclusionTaken together, these results suggest that the variation in the CB1R (i.e., rs2023239 SNP) may play a larger role in nicotine reinforcement compared to cue reactivity. This work provides impetus to further understand the physiological mechanisms that explain how CB1Rs influence nicotine dependence phenotypes.

Association of toll-like receptor polymorphisms with acquisition of HIV infection and clinical findings: A protocol for systematic review and meta-analysis.

Background:To find the relationship between toll-like receptor (TLR) gene variants and human immunodeficiency virus (HIV) infection and clinical findings, which could inform clinical decisions and vaccination strategies.Method:Four databases were searched for articles that were published on or before Jul.1, 2020. Review Manager 5.3 software was applied to perform meta-analysis to explore.Results:A total of 10 studies involving 20 genes, 3697 cases, and 6498 controls were included in this systematic review. TLR2 –196 to –174 Ins/Del (odds ratio [OR] = 1.562; P = .002), TLR4 rs4986790 (OR = 2.05; P = .002), TLR3 rs3775291 (OR = 0.25; P = .03), TLR7 rs179008 (P = .002), TLR7 rs2074109 (OR = 0.27, P = .019) were found associated with HIV infection. TLR2 –196 to –174, TLR4 rs4986790, TLR7 rs179008, TLR8 rs3764880, TLR9 rs352140 were found associated with clinical findings of HIV infection. We identified 5 case-control studies in meta-analysis, involving 695 cases and 729 controls on TLR7 rs179008 polymorphism, totaling 652 cases and 614 controls on TLR9 rs352140 polymorphism. In meta-analysis, we employed various genetic models. The T allele of TLR7 rs179008 was conferred the risk of HIV infection (T vs A: OR = 1.25, PA = .02). An increased risk of HIV infection was found for individuals with the TLR9 rs352140 GG genotype (GG vs AA: OR = 1.50, PA = .04).Conclusions:The systematic review indicated that TLR7 rs179008 T allele provides risk effects for HIV infection. TLR9 rs352140 GG genotype may associate with HIV infection.

Single nucleotide polymorphisms in sweet, fat, umami, salt, bitter and sour taste receptor genes are associated with gustatory function and taste preferences in young adults

Taste is a fundamental mechanism whereby compounds are detected orally, yet it is highly variable among individuals. The variability in taste that is attributable to genetics is not well-characterized despite its potential role in food selection, and therefore, eating habits that contribute to risk of overweight and obesity. In order to implicate measures of taste function and preference as potentially deterministic factors in adverse eating behaviors that lead to obesity, it must be shown that a relationship exists between genetic variation in taste receptor genes and psychophysical measures of taste in the absence high body mass index. The primary objective of this pilot study was to investigate the relationship between single nucleotide polymorphisms (SNPs) in taste receptor genes and 3 different psychophysical measures of taste in healthy young adults. Sweet, salt, umami, fat, sour, and bitter taste receptor gene SNPs were genotyped in 49 participants (ages 24.6 ± 0.6 years) who completed testing to determine oral detection threshold (DT), suprathreshold sensitivity (ST) and taste preference (PR). A simultaneous association test was conducted between each SNP and the 3 taste outcomes (DT, ST, and PR). Twelve SNPs were associated with at least one of the 3 taste outcomes. Associations were observed between SNPs in taste receptor genes and psychophysical measures of sweet, fat, umami, and salt taste. These results suggest that differences in interindividual psychophysical measures of tastes, namely DT, ST, and PR, may be partially attributed to genetic variation in taste receptor genes. Future studies are warranted to investigate if these findings have consequences for habitual dietary intake of foods that elicit these tastes.

Leptin receptor and fatty acid desaturase-2 gene variants affect fat, color and production profile of dry-cured hams

The effects of LEPR (rs709596309C > T) and FADS2 (rs321384923A > G) single nucleotide polymorphisms on production and quality attributes in purebred Duroc dry-cured hams were examined. As compared to LEPR-C– hams, the LEPR-TT hams had more intramuscular fat (+2.2% dry matter, P < 0.01). As a result, they showed higher saturated (+1.54%, P < 0.01) and lower polyunsaturated (−1.05%, P < 0.01) fatty acids content and were brighter (L*: +1.07, P < 0.05) and yellower (b*: +0.78, P < 0.01). The FADS2-A allele enhanced the C20:4n-6 to C18:2n-6 ratio but did not affect either fat content or color coordinates. However, hams carrying the FADS2-A allele reached the target weight loss earlier, thereby spending less time in seasoning (−8.4 d, P < 0.01). Thus, production batches could be arranged by genotype, with longer manufacturing times for fatter LEPR-TT and shorter times for FADS2-A− hams. These results confirm that genetic markers validated in raw pork are effective in dry-cured ham, but also stress that product-specific validations are still needed to unravel specific outcomes.

Association of vitamin D receptor and CYP2R1 mRNA expression with pulmonary tuberculosis

IntroductionThe vitamin D metabolic pathway has been shown to play a pivotal role in the pathogenesis of pulmonary tuberculosis (PTB), and vitamin D receptor (VDR) and CYP2R1 gene variation are known to affect vitamin D status. Hence, this study aimed to evaluate VDR and CYP2R1 mRNA expression in peripheral blood mononuclear cells (PBMCs) in PTB patients.Material and methodsWe measured VDR and CYP2R1 mRNA levels in 75 PTB patients and 63 healthy controls by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The associations of VDR and CYP2R1 mRNA levels with clinical characteristics and laboratory indexes of PTB patients were also examined in this study.ResultsCompared to healthy controls, the VDR mRNA level was significantly higher, and the CYP2R1 mRNA level was significantly lower in PBMCs from PTB patients (p = 0.047, p = 0.008, respectively). The CYP2R1 mRNA level in PTB patients with drug-resistant, unilateral tuberculosis foci was significantly higher than that in PTB patients without these clinical characteristics (p = 0.005, p = 0.048, respectively). In addition, our results demonstrated that the VDR mRNA expression level was positively correlated with erythrocyte sedimentation rate (ESR) (p = 0.045), while the CYP2R1 mRNA level was negatively correlated with ESR in PTB patients (p = 0.020).ConclusionsAltered VDR and CYP2R1 mRNA expression levels among PTB patients suggest their involvement in this disease.

Copy number variant analysis and expression profiling of the olfactory receptor-rich 11q11 region in obesity predisposition

Genome-wide copy number surveys associated chromosome 11q11 with obesity. As this is an olfactory receptor-rich region, we hypothesize that genetic variation in olfactory receptor genes might be implicated in the pathogenesis of obesity. Multiplex Amplicon Quantification analysis was applied to screen for copy number variants at chromosome 11q11 in 627 patients with obesity and 330 healthy-weight individuals. A ± 80 kb deletion with an internally 1.3 kb retained segment was identified, covering the three olfactory receptor genes OR4C11, OR4P4, and OR4S2. A significant increase in copy number loss(es) was perceived in our patient cohort (MAF = 27%; p = 0.02). Gene expression profiling in metabolic relevant tissues was performed to evaluate the functional impact of the obesity susceptible locus. All three 11q11 genes were present in visceral and subcutaneous adipose tissue while no expression was perceived in the liver. These results support the ‘metabolic system’ hypothesis and imply that gene disruption of OR4C11, OR4P4, and OR4S2 will negatively influence energy metabolism, ultimately leading to fat accumulation and obesity. Our study thus demonstrates a role for structural variation within olfactory receptor-rich regions in complex diseases and defines the 11q11 deletion as a risk factor for obesity.

Histamine H3 receptor gene variants associated with drug abuse in patients with cocaine use disorder.

Preclinical work revealed significant interactions between ligands of the histamine H3 receptor and different drugs of abuse. In the case of psychostimulants, the results reported are somewhat controversial and human data are still scarce, despite the fact that an inverse agonist of the H3 receptor (pitolisant) has reached the market after approval for the treatment of narcolepsy. We have studied associations between histamine H3 receptor gene variants and cocaine use disorder to increase the knowledge of the possible involvement of histamine H3 receptor in drug abuse. Seven single nucleotide polymorphisms of the histamine H3 receptor gene were genotyped by using a multiplexing assay in 248 samples of subjects with cocaine use disorder and 500 randomized samples of subjects representative of the Spanish population. The study of the epidemiological information associated to the samples revealed that subjects with cocaine use disorder broadly abused alcohol, tobacco and cannabinoids. Two single nucleotide polymorphisms (rs3787430 and rs74627870) were found significantly associated with the occurrence of addiction and one more (rs13042865) was specifically related to the severity of cocaine dependence within drug abusers. The associations found in this study further extend the hypothesis that histamine H3 receptor function could be relevant in drug abuse in general and cocaine addiction in particular.

Association between the group III metabotropic glutamate receptor gene polymorphisms and attention-deficit/hyperactivity disorder and functional exploration of risk loci

Existing evidence suggests that the group III metabotropic glutamate receptor (mGluR) gene variations are involved in attention-deficit/hyperactivity disorder (ADHD), but few studies have fully explored this association. We conducted a case-control study with 617 cases and 636 controls to investigate the association between functional single-nucleotide polymorphisms (SNPs) from the group III mGluR gene polymorphisms (GRM4, GRM7, GRM8) and ADHD in the Chinese Han population and initially explored the function of positive SNPs. The GRM4 rs1906953 T genotype showed a significant association with a decreased risk of ADHD (TT:CC, OR = 0.55, 95% CI = 0.40–0.77; recessive model, OR = 0.58, 95% CI = 0.43–0.78). GRM7 rs9826579 C showed a significant association with an increased risk of ADHD (TC:TT, OR = 1.81, 95% CI = 1.39–2.36; dominant model, OR = 1.74, 95% CI = 1.35–2.24; additive model, OR = 1.56, 95% CI = 1.24–1.97). In addition, compared with subjects with the rs1906953 TT genotype, subjects with of the CC genotype showed more obvious attention deficit behaviours and hyperactivity/impulsive behaviours. Dual-luciferase reporter gene assays showed that a promoter reporter with the rs1906953 TT genotype significantly decreased luciferase activity compared with the CC genotype. According to electrophoretic mobility shift assays, the binding capacity of rs1906953 T probe with nucleoprotein was lower than that of the rs1906953 C probe. Our results revealed the association of GRM4 rs1906953 and GRM7 rs9826579 with ADHD. Moreover, we found that rs1906953 disturbs the transcriptional activity of GRM4.

Polikistik Over Sendromu ve Obezite: FTO ve MC4R Gen Polimorfizmlerinin Rolü

Polikistik Over Sendromu (PKOS) etiyolojisi karmaşık olan multifaktöriyel bir endokrin bozukluktur. Ayrıca kadınlarda obezite ve tip 2 diyabet gelişim riskini arttıran metabolik bozukluklarla da ilişkilidir. Obezite/adipozite ve insülin direnci PKOS’lu kadınlarda oldukça sık karşılaşılan bir problemdir. İnsan genomunun ayrıntılı olarak incelendiği genom projelerinde obezite ve bazı hastalıklarla ilişkili çok sayıda gen ve genetik varyasyonların bulunduğu gösterilmiştir. Bu genler içerisinde yağ kütlesi ve obezite ile ilişkili gen (FTO) ve melanokortin-4 reseptör geni (MC4R) varyantları obezite, aşırı vücut ağırlığı ve tip 2 diyabet ile ilişkilidir. Bu nedenle FTO ve MC4R genlerinin obezite/adipozite gelişimine etkileri yoluyla PKOS ile ilişkili olabileceği öne sürülmektedir. Bu derleme makalede obeziteyle ilişkili bazı gen polimorfizmlerinin (FTO ve MC4R) PKOS ile ilişkisi incelenmiştir.

Differential distribution in vitamin D receptor gene variants and expression profile in Northeast Brazil influences upon active pulmonary tuberculosis.

Tuberculosis is an infectious disease with variable outcomes. This variability is due to host immune capacity in containing the infection process initiated by the Mycobacterium tuberculosis (MTB). Vitamin D is able to modulate a very specific immune response against MTB infection, and its action relies on vitamin D receptor (VDR) binding. Altered VDR forms may compromise vitamin D pathway and proper immune response after MTB infection. Herein we assessed the relationship of five potentially functional polymorphisms from VDR: rs2228570 FokI, rs11568820 Cdx-2, rs2248098, rs1540339 and rs4760648, with tuberculosis susceptibility. The SNP rs4760648 T/T was associated with differential susceptibility to tuberculosis (OR = 2.50, 95%CI = 1.20-5.36, p = 0.01). The SNP rs1540339 presented association to both T allele (OR = 0.55, 95%CI = 0.35-0.88, p = 0.01) and the T/T genotype (OR = 0.404, 95%CI = 0.20 - 0.78, p = 0.005). The FokI T allele was identified as associated to diminished susceptibility (OR = 0.67, 95% CI = 0.45-0.99, p = 0.04) to active TB, as well as T/T genotype (OR = 0.15, 95%CI = 0.04-0.45, p = 9.58 × 10-5). We also performed the expression analyses and observed a down-regulation of VDR in patients (-10.717 FC, p = 8.42e-12), and according to the presence of associated FokI SNP, we observed that the C/T and T/T genotypes presence increases VDR expression (+ 1.25 and + 2.35 FC, p = 0.425 and p = 0.506, respectively). This study shows that vitamin D receptor variants can influence upon pulmonary tuberculosis susceptibility and VDR mRNA levels are decreased in those patients.

Leptin receptor gene polymorphisms c.668A>G and c.1968G>C in Sudanese women with preeclampsia: a case-control study

BackgroundLeptin receptor gene (LEPR) variants may affect the leptin levels and act as a risk factor for preeclampsia. Two LEPR gene missense variants rs1137101 (c.668A>G) and rs1805094 (c.1968G>C) were investigated in Sudanese women with preeclampsia.MethodsA matched case-control study (122 women in each arm) was conducted in Saad Abualila Maternity Hospital in Khartoum, Sudan from May to December 2018. The cases were women with preeclampsia and the controls were healthy pregnant women. Genotyping for LEPR gene variants c.668A>G and c.1968G>C was performed using polymerase chain reaction-restriction fragment length polymorphism. Logistic regression models (adjusted for age, parity, body mass index and hemoglobin level) were conducted.ResultsGenotype frequency of LEPR gene variants c.668A>G and c.1968G>C was in accordance with Hardy–Weinberg equilibrium (P > 0.05) in the controls. Allele G in LEPRc.668A>G variant was significantly more frequent in the cases compared with the controls [43.4% vs. 10.2%; OR = 6.44; 95%CI (3.98–10.40); P < 0.001]. In variant LEPRc.668A>G, genotype AG was the prevalent genotype in the cases compared with the controls, and it was significantly associated with preeclampsia risk [37.7% vs. 15.5%; AOR = 3.48; 95%CI (1.15–10.54); P = 0.027]. Likewise, the GG genotype was the second most common genotype in the cases compared with the controls, and was associated with preeclampsia risk [24.6% vs. 2.5%; AOR = 14.19; 95%CI (1.77–113.76); P = 0.012]. None of the LEPRc.1968G>C variant genotypes were associated with preeclampsia. The CC genotype was not detected in neither the cases nor the controls. The haplotype A-G 70.1% was the prevalent haplotype in this population, and it significantly protected against preeclampsia [OR = 0.14; 95%CI (0.09–0.23); P < 0.001]. However, the haplotype G-G 26.8% was significantly associated with preeclampsia risk [OR = 6.70; 95%CI (4.16–11.05); P < 0.001]. Both variants c.668A>G and c.1968G>C were in strong linkage disequilibrium (D′ = 1, r2 = 0.012).ConclusionsOur data indicate that the rs1137101 (c.668A>G) variant and G-G haplotype may independently associate with the development of preeclampsia.

Correlating Schizophrenia with DRD3 Ser9Gly or HTR2 Receptor Gene Variants by using RFLP Method

Genetic polymorphism in many candidates associated with psychiatric disorder and Schizophrenia (SCZ). The current research is directed to see if the polymorphisms of Dopamine Receptor D3 (DRD3) or of the 5-Hydroxytryptamine Type 2A (HTR2A) genes is related to SCZ patients. From those admitted to Al Rasheed Hospital, fifty patients with SCZ (half of them are males and the other half are females), in addition to control group (25 healthy individuals) were included in this study. Blood samples from each individual in both, healthy and control groups were collected, DNA was extracted. Specific primers for exon1 and another for exon 2 have been used to amplify the genes of DRD3 receptor and HTR2A. The data generated in this study indicated significant positive association between T102C polymorphism of HTR2A A1804G transition and DRD3 gene sequence, that resulted in the substitution of Ser9Gly amino acid Iraqi SCZ patients.

Identification of novel advanced glycation end products receptor gene variants associated with colorectal cancer in Tunisians: A case-control study.

A central role for advanced glycation end products (AGE) and their receptor (RAGE) in the pathogenesis of multiple cancer types, including colorectal cancer (CRC) was reported. We investigated the association between CRC and rs2853807, rs77170610, rs184003, rs1035798, rs2070600, rs1800684, rs1800624, and rs1800625 RAGE gene (AGER) polymorphic variants. Study subjects comprised 293 CRC patients [186 colon cancer (CC) and 107 rectal cancer (RC)] patients), and 264 age-, gender-, BMI-, and ethnicity-matched controls. Minor allele frequency (MAF) of rs77170610 and rs1800625 were significantly lower, while MAF of rs1035798 was significantly higher in CRC patients compared to control subjects, which was associated with reduced and increased risk of CRC, respectively; MAF of the remaining variants was comparable between CRC patients and controls. Significant difference in the distribution of rs2853807 and rs77170610 genotypes was seen between CRC patients and controls, with both variants associated with decreased risk of CRC. Comparison of the distribution of minor allele-carrying genotypes in CC and RC patient subgroups revealed lack of significant difference in the distribution of these genotypes between the patient subgroups. In view of the lack of LD between rs2853807 and rs77170610 with other variants, six-locus (rs184003, rs1035798, rs2070600, rs1800684, rs1800624, rs1800625) haplotypes were constructed. Haplotype analysis did not identify any specific 6-locus AGER haplotype associated with CRC. In conclusion, AGER gene rs2853807 and rs77170610 variants rs77170610 are associated with altered risk of CRC in Tunisians, but with no discrimination between CC and RC types.

Influence of dopamine receptor gene on eating behaviour and obesity in Malaysia

PurposeObesity is still an issue worldwide with a high prevalence rate in spite of countless health awareness campaigns being held by both government and non-profit organisations. This issue is also faced in Malaysia. Thus, this is indeed to study on the risk factor of obesity, especially at the genetic aspect of eating behaviour which is still lacking and inconclusive. This study was to investigate the influence of dopamine type 2 receptors (DRD2) gene variants (ANKK1/DRD2 Taq1A, DRD2 Taq1B and DRD2 Taq1D) on eating behaviours [cognitive restraint eating (CR), emotional eating (EE) and uncontrolled eating (UE)] as well as to obesity. MethodsThe study consisted of 394 subjects (125 males and 269 females) who studied or worked in University Tunku Abdul Rahman (UTAR), Malaysia. Eating behaviour scores were assessed by using the Three-Factor Eating Questionnaire-R18 (TFEQ-R18). Body mass index (BMI) of the participants was taken to evaluate obesity status. Genotyping of Taq1 gene polymorphisms was carried out using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) using the genomic DNAs extracted from mouthwash samples. ResultsThere is no significant association between DRD2 gene variants with obesity (p > .05). However, ANKK1/DRD2 Taq1A gene polymorphism demonstrated a significant difference in EE score (p < .05). Nevertheless, all three Taq1 gene variants showed no significant difference in CR and UE score (p > .05). ConclusionsThis study postulated that ANKK1/DRD2 Taq1A gene variant might have an influential effect on emotional eating among Malaysian adults. Besides, findings demonstrated no association of dopamine receptor gene variants with obesity. However, the role of eating behaviour in leading to obesity was yet inconclusive, and further study is required.

Elucidating roles of the Rag1 N-terminus and RAG DSBs in shaping the cellular response to TCRa recombination

Abstract The RAG1/RAG2 (RAG) endonuclease generates lymphocyte antigen receptor gene diversity via V(D)J recombination. The large numbers of V, D, and J segments and inherent imprecision in repair of RAG DNA double strand breaks (DSBs) together establish a vast diversity of antigen receptor specificities, including self-reactive receptors. Mechanisms have evolved to negatively select self-reactive cells and inhibit autoimmunity. In humans, deletion of the RAG1 N-terminus causes Omenn Syndrome, a fatal immunodeficiency with ab T cell-based autoimmunity. We discovered impaired negative selection in a spontaneous homozygous Rag1 mutant mouse with loss of the Rag1 N-terminus. This Rag1 region, which is not required for V(D)J recombination, has intrinsic ubiquitin ligase activity and interacts with another ubiquitin ligase and a kinase. We hypothesize the RAG1 N-terminus signals from RAG DSBs induced during TCRa recombination to shape the thymocyte proteome and enhance negative selection. To test our hypothesis, we have made mice whose thymocytes lack RAG DSBs or harbor RAG DSBs induced by wild-type Rag1 or mutant Rag1 lacking the N-terminus or intrinsic ubiquitin ligase activity. Our preliminary data suggest that RAG DSBs and distinct RAG1 N-terminus activities up-regulate expression of Zap70, an intracellular protein that transmits TCR signals, and CD80, a transmembrane protein that co-stimulates T cells engaging antigen. These data are consistent with a model wherein the RAG1 N-terminus facilitates negative selection through stimulating TCR signaling in thymocytes that bind self-antigens presented by thymocytes, dendritic cells, or thymic epithelial cells.

Adrenocortical attunement, reactivity, and potential genetic correlates among parent-daughter dyads from low-income families.

Examining the multitude of influences on the development of adolescent stress responses, especially among low-income families, is a critical and understudied topic in the field. The current study examined cortisol attunement between adolescent girls and parents (mostly mothers) from predominantly low-income, single parent, ethnic minority families before and after an in-laboratory disagreement discussion task. The sample consisted of 118 adolescents (Mage =13.79years, 76.3% ethnic minorities, 23.7% European Americans) and primary caregivers (Mage =40.62years; Mdn yearly income = $24,000; 43.2% single parents; 50% living below poverty line). We investigated oxytocin receptor (OXTR rs53576) gene variations as a potential contributor to attunement within the dyad. Results showed that parents and adolescents showed stress system attunement across the disagreement task, but that parent and adolescent oxytocin receptor genotype did not impact attunement. Future studies should detail biological factors that contribute to the calibration of stress response systems of adolescents across a variety of samples, particularly those experiencing a combination of stressors.

A Study to Explore the LDLR Gene Polymorphisms Contribute to Atorvastatin Response in a Sample of Iraqi Population with Atherosclerotic Coronary Artery Disease

Genetic factors will determine the higher variability, which found in response to lipid reduction treatment (statins). However, due to ethnicity the frequency and effect of single nucleotide polymorphisms (SNPs) may differ. The main aim of lipid lowering medical treatment is to eventually prevent the endogenous production of cholesterol through inhibition of HMG-CoA reductase, The resulting decrease in hepatocyte cholesterol concentration triggers up-regulation of low-density lipoprotein (LDL)-receptor expression by inducing sterol regulatory element-binding protein (SREBP) 2 cleavage, as SREBP-2 activates LDL receptor transcription. The aim of this study was to evaluate the effects of low density lipoprotein receptor (LDL-R) gene variants (rs200727689; rs72658860) in response to atorvastatin treatment in atherosclerotic coronary artery disease (ACAD) in a sample of Iraqi patients. The genetic polymorphisms of rs200727689 and rs72658860 were studied in patients undergoing coronary angiography (CAG). One hundred Iraqi patients include 52 patients treated with 20mg/day and 48 patients treated with 40mg/day, In addition, 100 apparently healthy subjects were genotype for these SNP by the thermal profile of allelic discrimination methods used Real Time PCR (RT-PCR) assay. A significant increase in A allele frequency (rs200727689) compared with controls for total ACAD patients (43% vs 23.5%; OR= 2.46; 95% C.I: 1.60-3.77; p=0.000). For (rs72658860) SNP, among total patients the A allele also increased the frequency substantially compared with the controls (40.5% vs 23.5%; P=0.0003; OR= 2.22; 95% C.I: 1.44 -3.41). In the patients who were treated with atorvastatin, SNP rs72658860 AA genotype significantly affected the response of atorvastatin in dose 20mg compared with 40mg. The result showed in AA genotype of (rs200727689) SNP a reduction in TC concentrations (277.55±108.38 vs 326.99±63.56) and LDL-C concentrations (198.33±100.0 vs 250.01±62.52) in sera compared with GG genotype in patients treated with 20 mg atorvastatin, although, none in all parameters statistically significant differences.

Melanocortin 4 receptor (MC4R) gene variants in children and adolescents having familial early-onset obesity: genetic and clinical characteristics.

Melanocortin 4 receptor gene plays an important role in food intake, energy balance, and weight control. The autosomal dominantly inherited MC4R variants cause obesity by causing hyperphagia and decreased sense of satiety. Homozygous variants are rarely reported, and they cause earlier/severe obesity. Our objective is to determine the MC4R gene variant frequency in children and adolescents with familial early-onset obesity. One hundred thirty-nine children and adolescents (57 girls/82 boys) whose weight increase started before the age of 5 years and who had early-onset obesity in at least one of their first-degree relatives were included in the study. Obesity is defined as body mass index (BMI) of ≥ 95th percentile, and as extreme obesity is defined if the BMI ≥ 120% of the 95th percentile or ≥ 35 kg/m2. Children having genetic syndromes associated with obesity and mental retardation or taking drugs that promote changes in eating behavior or weight were excluded from the study. Coding region of the MC4R gene was sequenced by using the Illumina MiSeq Next Generation Sequencing System. The mean age of the patients was 7.3 ± 3.7 years, and the mean BMI SDS was 3.7 ± 0.7. While 118 patients (85%) were prepubertal, 21 patients (15%) were pubertal. Seven different variants were identified in 12 patients by giving a variant detection rate of 8.6%, of these five were previously identified missense variants p.N274S, p.S136F, p.V166I, p.R165W, and p.I291SfsX10. One homozygous variant p.I291SfsX10 (c.870delG) was detected in a severely obese 2-year-old boy, and other variants were heterozygous. Two novel variants were found: p.M200del and p.S188L. By using the in silico analysis software, these novel variants were predicted to be disease causing.Conclusion: MC4R gene variants are quite common in childhood obesity in Turkish population. Screening the variants in MC4R gene is necessary in patients with severe childhood-onset obesity. In such patients, comorbidities of obesity can be seen from early years.What is known• The frequency of MC4R mutations in obese patients was approximately 0–6.3%.What is new• In obese Turkish pediatric population, unlike other European countries, MC4R gene variants are quite common as we found a variant rate of 8.6%• We believe it is necessary to screen the variants in MC4R gene in patients with severe childhood-onset obesity and who had early-onset obesity in at least one of their first-degree relatives in Turkish population.

Association of estrogen receptor gene variants (ESR1 and ESR2) with polycystic ovary syndrome in Tunisia.

SNV (single nucleotide variation) in estrogen receptor (ESR1 and ESR2) genes are susceptibility markers for complex diseases, such as cancer, metabolic disorders and women infertility. We explored six widely used SNVs in ESR1 (rs2234693, rs9340799, rs3798577, rs3020314) and ESR2 (rs1256049, rs4986938) in polycystic ovary syndrome (PCOS) in women from Tunisia (n=254) compared to controls (n=170). Genotyping was performed by RFLP-PCR or real-time PCR and analyzed in GoldenHelix statistical package. Logistic regression revealed association of rs2234693, rs3798577 and rs3020314 (ESR1) and rs1256049 (ESR2), the association of rs2234693 (C/T) being the strongest with P<4.81×10-6, 2.88×10-5 after Bonferroni correction, OR 0.31, 95%CI (0.18-0.53)). Correlations were found with LH, LH/FSH or hyperandrogenism and even more significant with metabolic syndrome (rs9340799) and hyperglycemia (rs3798577). Among 14 haplotypes reconstructed in ESR1gene, four haplotypes (H1 to H4) were associated with PCOS the strongest being that of H1 (P<0.002) supported by Bonferroni (P<0.033) and permutation tests (P<4 x10-4). In haplotype trend regression, concordant correlations were found with insulin resistance (P<0.033) for H2 and with high blood pressure for H3 (P<0.048). While these data revealed influential role on metabolic rather and hormonal features of PCOS, the association of rs2234693 was the strongest among all ethnic populations studied thus far giving a new insight on estrogen receptor gene variation in distant North African populations and their role in metabolic alteration of PCOS.

Lipids profile in vitamin D insufficient/deficient subjects with different genotypes of vitamin D receptor gene

Background. Recent studies have demonstrated possible association between vitamin D deficiency and atherogenic dyslipidemia. However, there are practically no results from Russian investigations in this field. Objective. To assess serum lipids in women carrying various vitamin D receptor (VDR) gene variants. Design and methods . The study included 697 women aged between 35 to 55 years (mean age 43,4 ± 0,3 years). Anthropometric data including height, waist circumference, body mass index were measured. Serum lipid profile, 25-hydroxyvitamin D (25(OH)D) level and four VDR gene polymorphisms BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236), and FokI (rs2228570) were evaluated. The results showed high prevalence of abdominal obesity, dyslipidemia, vitamin D insufficiency/deficiency in the study group and 2,6 increased risk of high-density lipoprotein (HDL) cholesterol reduction in women with vitamin D deficiency. There were no differences in serum 25(OH)D between VDR genotypes. GG (BB) genotype carriers of BsmI (rs1544410) demonstrated higher triglyceride levels than subjects with GA, AA (Bb, bb) genotypes. Women with TT (AA) и TG (Aa) genotypes of ApaI (rs7975232) had higher total cholesterol and low-density lipoprotein (LDL) cholesterol levels compared to GG (aa) genotype carriers. Conclusions. The study revealed the associations between low vitamin D status and decreased HDL cholesterol as well as between BsmI (rs1544410) and ApaI (rs7975232) VDR genotypes and atherogenic dyslipidemia.