TT Homozygotes Research Articles

Association of the GRIK4 rs1954787 polymorphism with clinical response in antidepressant-treated depressed patients: results from a prospective cohort and meta-analysis.

Major Depressive Disorder (MDD) is the leading cause of disability worldwide. Genetic factors influence the effect of its main treatment option, antidepressant drugs (ATD). The GRIK4 rs1954787(T>C) genetic polymorphism was associated with response following 1-3 months of ATD treatment in some studies, but not others. We aimed to analyze its association with clinical outcomes in a cohort of 6-month ATD-treated patients and meta-analysis. Clinical data were obtained at baseline and after 1 (M1), 3 (M3), and 6 (M6) months of ATD treatment in 390 patients of the METADAP cohort. Mixed-effects models were used to assess the association of the GRIK4 rs1954787 polymorphism with the Hamilton Depression Rating Scale (HDRS) score and response and remission rates across time. Meta-analyses of ATD treatment response were performed with previously meta-analyzed data and METADAP. Compared to C allele carriers at M3 (n = 200), TT homozygotes at M3 (n = 66) had higher HDRS scores (coef = 3.37, 95% CI [1.30-5.54], Padj = 0.0046) and lower remission rates (OR = 0.36, 95% CI [0.16-0.76], Padj = 0.029). At M6, greater differences between TT homozygotes (n = 53) and C allele carriers (n = 152) were observed for HDRS scores (coef = 4.68, 95% CI [2.17-7.18], Padj = 0.00091) and remission rates (OR = 0.26, 95% CI [0.12-0.54], Padj = 0.0016). Meta-analyses of response were significant when comparing C vs T alleles (OR = 1.31, 95% CI [1.06-1.62], P = 0.014) and CC vs TT genotypes (OR = 1.63, 95% CI [1.10-2.38], P = 0.019). Altogether, our results support an association of the GRIK4 rs1954787(T>C) polymorphism with clinical improvement following ATD treatment. This association should be further assessed in other longitudinal studies. Its position within the glutamatergic system may help in understanding the mechanism of ATD action.

The effect of the M235T polymorphism of the angiotensinogen gene on the office blood pressure during therapy with angiotensin II receptor blockers

Aim. To study the pharmacodynamic parameters of the effectiveness of therapy with angiotensin II receptor blockers in the form of monotherapy and as part of combination drugs in patients with hypertension, depending on the genetic characteristics of patients — the M235T polymorphism of the angiotensinogen gene (AGT).Material and methods. The study included 179 patients in the Moscow region with newly diagnosed hypertension of 1-2 degrees, among whom 141 (78.8%) women and 38 (21.2%) men aged 32 to 69 years, who were randomly assigned to irbesartan and valsartan groups in the form of mono- or combination therapy with hydrochlorothiazide by a simple randomization method. After 3 weeks of pharmacotherapy, the presence of rs699 (C4072T, M235T) genetic polymorphism of the AGT was determined.Results. Homozygotes СС with the genetic polymorphism M235T of the AGT treated with valsartan had a statistically significantly higher frequency of achieving target blood pressure figures after 3 weeks of pharmacotherapy compared with TT homozygotes (p=0.006) and a statistically significantly lower frequency of the need to increase the dose of the drug compared with heterozygotes and TT homozygotes (p=0.047 and 0.006, respectively). Among patients treated with irbesartan, there was no statistically significant association of the M235T polymorphism genotype of the AGT with these indicators.Conclusion. The data obtained may indicate a faster and more stable antihypertensive effect in homozygotes of CC and TT of the genetic polymorphism M235T of the AGT. When personalizing hypertension therapy for patients of the Moscow region, carriers of homozygous CC and TT genotypes of the M235T genetic polymorphism of the AGT for more effective achievement of target blood pressure figures, it is advisable to recommend valsartan as a starting therapy in the form of mono- or twocomponent therapy, depending on the degree of hypertension.

TCF7L2 Polymorphism rs7903146 (C/T) and Gestational Diabetes Influence on Obstetric Outcome: A Romanian Case-Control Study.

Gestational diabetes mellitus (GDM) is one of the most frequent predictors of obstetric outcome among Romanian pregnant women. Thus, we aimed to investigate the role of rs7903146 (C/T) TCF7L2 gene polymorphism in the presence of GDM and to evaluate the influence on maternal-fetal outcomes in a cohort of pregnant women from Northern Transylvania. Our prospective case-control study was performed in a tertiary maternity center on 61 patients diagnosed with GDM and 55 normal pregnant patients. The patients were genotyped for rs7903146 (C/T) polymorphism of the TCF7L2 gene using the PCR-RFLP method between 24 and 28 weeks of gestation. The minor T allele was associated with a high risk of developing GDM (OR 1.71 [95% CI 0.82-3.59]) if both heterozygote and homozygote types were considered. Also, a higher risk of developing GDM was observed in homozygous carriers (OR 3.26 [95% CI 1.10-9.68]). Women with the TT genotype were more likely to require insulin therapy during pregnancy than other genotypes with a 5.67-fold increased risk ([1.61-19.97], p = 0.015). TT homozygote type was significantly associated with fetal macrosomia for birth weights greater than the 95th percentile (p = 0.034). The homozygous TT genotype is associated with an increased risk of developing GDM. Also, rs7903146 (C/T) TCF7L2 variant is accompanied by a high probability of developing insulin-dependent gestational diabetes mellitus (ID-GDM). The presence of at least one minor T allele was associated with a higher risk of fetal macrosomia.

Effect of diet and MC4R genotype on nutrient digestibility and nitrogen balance in Kacang goats

This study aims to determine the effect of the relationship between feed treatment and Melanocortin 4 receptor (MC4R) genotypes on nutrient digestibility and nitrogen balance in Kacang goats. Blood samples were collected from 20 Kacang goats, and genomic DNA was extracted by using a Geneaid isolation kit. Polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) was used to genotype blood samples at the SNP position g.1079C/T cut by the KpnI enzyme. A 2 × 3 factorial design with two diet factors (diets 1 and 2) and three genotypes (homozygotes CC and TT and heterozygote CT) was used. The diet 1 and 2 groups comprised 4 goats with the TT genotype, 4 goats with the CT genotype and 2 goats with the CC genotype. Diet 1 contained an additional 400 g of concentrate with 11.25% crude protein (CP) and 55.88% total digestible nutrient (TDN) and diet 2 contained a total mixed ration containing 12.46% CP and 67.92% TDN. Results demonstrated that diet and MC4R genotype had a nonsignificant interactive effect (P>0.05) on nutrient digestibility, N balance and blood composition. However, feed factor shown a significant result (P<0.05) on EEI, NDFI, DM, CP, EE, NDF, DM, CP, EE and NDF on TT genotype (P0) with the highest level than CC and CT genotype (P1). The P0 goat group absorbs a lot of nitrogen in the body, however the P1 goat group is able to utilize the nutrient efficiently in the body. Kacang goats with the TT genotype can be selected as livestock that excel in utilizing nutrients in feed

Association of Four Interleukin-8 Polymorphisms (-251 A>T, +781 C>T, +1633 C>T, +2767 A>T) with Ovarian Cancer Risk: Focus on Menopausal Status and Endometriosis-Related Subtypes.

Interleukin-8 (IL-8) is involved in the regulation of inflammatory processes and carcinogenesis. Single-nucleotide polymorphisms (SNPs) within the IL-8 gene have been shown to alter the risks of lung, gastric, or hepatocellular carcinomas. To date, only one study examined the role of IL-8 SNPs in ovarian cancer (OC), suggesting an association between two IL-8 SNPs and OC risk. In this study, we investigated four common IL-8 SNPs, rs4073 (-251 A>T), rs2227306 (+781 C>T), rs2227543 (+1633 C>T), and rs1126647 (+2767 A>T), using the restriction fragment length polymorphism (PCR-RFLP) technique. Our study included a cohort of 413 women of Central European descent, consisting of 200 OC patients and 213 healthy controls. The most common (73.5%) histological type was high-grade serous OC (HGSOC), whereas 28/200 (14%) patients had endometriosis-related (clear cell or endometrioid) OC subtypes (EROC). In postmenopausal women, three of the four investigated SNPs, rs4073 (-251 A>T), rs2227306 (+781 C>T), and rs2227543 (+1633 C>T), were associated with OC risk. Furthermore, we are the first to report a significant relationship between the T allele or TT genotype of SNP rs1126647 (+2767 A>T) and the EROC subtype (p = 0.02 in the co-dominant model). The TT homozygotes were found more than twice as often in EROC compared to other OC subtypes (39% vs. 19%, p = 0.015). None of the examined SNPs appeared to influence OC risk in premenopausal women, nor were they associated with the aggressive HGSOC subtype or the stage of disease at the initial diagnosis.

The Regulatory Variant -108C/T in the Promoter of Paraoxonase 1 (PON1) Gene has a More Important Role in Regulating PON1 Activity Compared to rs3735590 in 3'-UTR in Patients with Coronary Artery Disease.

This study aimed to assess the serum activity of paraoxonase 1 (PON1) in patients with coronary artery disease (CAD) based on two genetic variants including the -108C/T variant in the promoter region and the rs3735590 variant in the binding site of miR-616 at the 3'-UTR of the PON1 gene. A total of 140 subjects who exhibited clinical symptoms of CAD underwent diagnostic coronary angiography. The patients with CAD were further categorized into two groups: single-vessel disease (SVD) and multi-vessel disease (MVD). The study variants were genotyped using the restriction fragment length polymorphism (RFLP) technique after polymerase chain reaction amplification. After adjusting for age, gender, body mass index, metformin, and statin usage, a significant association was observed between the -108C/T variant and PON1 activity (P < 0.001). In the sub-groups of both SVD and MVD, individuals with the TC+CC genotypes exhibited significantly higher PON1 activity compared to TT homozygotes (P = 0.001 for SVD and P = 0.01 for MVD). As for the rs3735590 variant, individuals with the A allele (GA+AA genotypes) had higher PON1 activity compared to those with the GG genotype in both the SVD and MVD groups, although the results did not reach statistical significance. Our study findings indicate a significant decrease in PON1 activity among patients with obstructive CAD. Notably, our results suggest that the -108C/T variant exerts a greater influence on PON1 activity compared to the rs3735590 variant. These findings highlight the crucial role of the -108C/T variant in modulating PON1 activity within the context of atherosclerosis.

Association Between AIRE Polymorphisms rs870881(C>T), rs1003854(T>C) and Rheumatoid Arthritis Risk: A Hungarian Case-control Study.

Autoimmune regulator (AIRE) is a transcription factor that plays pivotal role in controlling autoimmunity. In the thymus, it supports the presentation of peripheral tissue antigens to developing T cells, where recognition of these self-antigens negatively selects the autoimmune naïve T-cells by central tolerance. Studies demonstrated that single-nucleotide polymorphisms (SNPs) in AIRE alter transcription and propagate clonal survival of autoimmune T cells, therefore increase susceptibility to autoimmune diseases. This study intended to identify SNPs in exon and intron sequences that determine AIRE transcription, where their genotypes are associated with rheumatoid arthritis (RA) risk and clinical parameters. After a thorough in silico research, we enrolled 100 patients with RA and 100 healthy controls to analyze the association of SNP rs870881(C>T) and rs1003854(T>C) in AIRE coding sequence with RA risk by using five different genetic models and selected clinical parameters. Multiplex quantitative polymerase chain reaction was used to determine allelic discrimination of SNPs. RA risk was assessed by odds ratios (ORs) and confidence intervals (CIs). In a recessive model of rs878081, minor allele TT homozygotes were associated with RA (p=0.032, OR=5.44, 95%CI=1.16-25.52); in a recessive model of rs1003854, minor allele CC homozygotes were associated with RA (p=0.047, OR=4.84, 95%CI=1.02-23.02). Higher C-reactive protein (CRP) levels in patients with RA were significantly associated with minor allele homozygotes in recessive and codominant genetic models (p=0.029 and p=0.043, respectively) of rs1003854. Genotypes for minor alleles of rs878081 and rs1003854 might be involved in RA pathogenesis and risk prediction.

Possible effect of OAS1 and TMPRSS6 but not DPP4 and ZNF335 polymorphisms on COVID-19 severity in the Czech population.

The acute respiratory syndrome, known as COVID-19, is characterised by high morbidity and increased mortality. Genetic factors may partially explain the differences in susceptibility to and severity of COVID-19. We have analysed common functional polymorphisms within the OAS1 (rs4767027), TMPRSS6 (rs855791), DPP4 (rs3788979), and ZNF335 (rs3848719) genes in SARS-CoV-2 positive subjects (n = 521, different disease severity) and in population controls (n = 2,559 subjects, COVID-19 status unknown). Neither DPP4 nor ZNF335 were associated with disease susceptibility or severity in the Czech population in any of the models used for calculation. T allele carriers of the OAS1 polymorphism seem to be protective against symptomatic COVID-19 (p = 0.002 calculated for trend; asymptomatic, symptomatic, hospitalised). Similarly, within the TMPRSS6, minor TT homozygotes associated with lower plasma Fe concentrations were underrepresented in the overall patient group (p = 0.044; OR = 0.77, 95% CI: 0.59-0.99), and the difference was mainly driven by the severe COVID-19 subjects. In general, risky homozygotes of these two polymorphisms were less frequent than expected in the group of hospitalised COVID-19 survivors. Common variants within OAS1 (rs4767027) and TMPRSS6 (rs855791) play some role in COVID-19 pathology in the Czech Caucasian population. Whether the depletion of minor allele carriers of these two variants is associated with increased COVID-19 mortality, needs to be analysed in an external confirmatory study.

Polymorphisms in the Runx2 and osteocalcin genes affect BMD in postmenopausal women: a systematic review and meta-analysis.

Runx2 and osteocalcin have pivotal roles in bone homeostasis. Polymorphism of these two genes could alter the function of osteoblasts and consequently bone mineral density (BMD). Attempts to understand the relationship between these polymorphisms and BMD in postmenopausal women across a variety of populations have yielded inconsistent results. This meta-analysis seeks to define the relationship between these polymorphisms with BMD in postmenopausal women. Eligible studies were identified from three electronic databases. Data were extracted from the eligible studies (4 studies on Runx2 and 6 studies on osteocalcin), and associations of Runx2 T > C and osteocalcin HindIII polymorphisms with BMD in postmenopausal women were assessed using standard difference in means (SDM) and 95% confidence intervals (CI) as statistical measures. A significant difference in the lumbar spine (LS) BMD in postmenopausal women was observed between the TT and CC homozygotes for the Runx2 T > C (SDM = -0.445, p-value = 0.034). The mutant genotypes (CC) showed significantly lower LS BMD in comparison to wild type genotypes under recessive model of genetic analysis (TC + TT vs. CC: SDM = -0.451, p-value = 0.032). For osteocalcin, HindIII polymorphism, the mutant genotypes (HH) was associated with significantly higher BMD for both LS and femoral neck (FN) than the wild type (hh) homozygotes (SDM = 0.152, p-value = 0.008 and SDM = 0.139, p-value = 0.016 for LS and FN, respectively). There was no association between total hip (TH) BMD and the osteocalcin HindIII polymorphism. Runx2 T > C and osteocalcin HindIII polymorphisms influence the level of BMD in postmenopausal women and may be used as predictive markers of osteoporosis.

Associations of TNF-RII rs1061622 With Post-Traumatic Stress Disorder and Their Interplays on Serum Lipids Levels in Adolescents.

To verify effects of rs1061622 at tumor necrosis factor-α receptor II (TNF-RII) gene (TNF-RII) on post-traumatic stress disorder (PTSD) and its interactive effects with PTSD on serum lipids levels in adolescents. PTSD was measured by PTSD Checklist-Civilian Version (PCL-C) in 699 adolescent survivors at 6 months after Wenchuan earthquake in China. A polymerase chain reaction and restriction fragment length polymorphism assay were utilized for TNF-RII rs1061622 genotyping followed by verification using DNA sequencing. Serum triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol were tested using routine methods. G (deoxyguanine) allele carriers had higher PCL-C scores than TT (deoxythymidine) homozygotes in female subjects. Female adolescents had higher PCL-C scores than male subjects in TT homozygotes. Predictors of PTSD prevalence and severity were different between G allele carriers and TT homozygotes. Subjects with PTSD had lower TG, TG/HDL-C, TC/HDL-C, and higher HDL-C than adolescents without PTSD in male G allele carriers. G allele carriers had higher TG/HDL-C and TC/HDL-C than TT homozygotes in male adolescents without PTSD, and lower TG and TG/HDL-C in male PTSD patients. G allele carriers had higher TG than TT homozygotes only in female adolescents without PTSD. These results suggest reciprocal actions of TNF-RII rs1061622 with other factors on PTSD severity, interplays of TNF-RII rs1061622 with PTSD on serum lipid levels, and novel treatment strategies for PTSD and comorbidities of PTSD with hyperlipidemia among adolescents with different genetic backgrounds of TNF-RII rs1061622 after experiencing traumatic events.

The impact of duration and control of type 1 diabetes mellitus on microvascular function is strongly modified by the gene for connexin 37

Abstract Introduction Type 1 diabetes mellitus (T1DM) is almost inevitably accompanied by microvascular dysfunction. This could be responsible for cardiovascular events and is supposed to be caused mainly by long-term exposure to hyperglycemia. Nevertheless, relationship between duration and control of T1DM with microvascular complications can be modified by genetic factors; one of frequently discussed candidate genes is connexin37 (cx37), namely its rs1764391 (C1019&amp;gt;T (Pro319&amp;gt;Ser) polymorphism. We already observed sex specific association between cx37 polymorphism with macrovascular changes but also with retinopathy, neuropathy and diabetic foot. In the recent study, we analyzed if the impact of duration and control of T1DM on directly measured microvascular function is modified by cx37 gene polymorphism. Methods In 235 men and 227 women with T1DM (mean age 43.6 ± 13.6 years; mean duration of diabetes 22.1 ± 11.3 years) wide spectrum of clinical, laboratory and hemodynamic parameters was measured. Establishment of microvascular function measured by photoplethysmography (detection of blood volume changes in the microvasculature in lower extremities) and calculated as Oliva/Roztocil index (ORI), was analyzed. Cx37 gene polymorphism was measured by PCR-RFLP. The correlation (Pearson’s correlation coefficient) between duration of T1DM and ORI was calculated including analysis of potential modification by control of diabetes (HbA1c) and by cx37 gene polymorphism and standardized for potential confounders (sex, age, smoking, presence of hypertension, central obesity …) by multiple regression. The analysis was conducted separately for duration of T1DM below (n=256) and above (n=206) 20 years as the linear relationship between ORI and T1DM duration tends to change accordingly. Results In patients with T1DM, distribution of Cx37 genotypes did not differ from the already described populations (TT/CT/CC: 9.7/44.4/45.9%). In patients with satisfactory control of diabetes (HbA1c&amp;lt;53 mmol/mol; n=105) we detected worsening (increase) of ORI with duration of diabetes only in TT homozygotes and CT heterozygotes for duration of at least 20 years (r=0.6, p=0.006), while in patients with unsatisfactory control (HbA1c&amp;gt;60 mmol/mol;n=270), we detected worsening of ORI with duration of diabetes only in CC homozygotes, both for duration 0-20 years (r=0.35, p=0.03) and for duration of at least 20 years (r=0.47, p=0.03). Conclusion Microvascular function in satisfactory controlled T1DM was worsening with diabetes duration only in T allele carriers of Cx37 gene, the worsening was detected only for patients with duration longer than 20 years. However, if T1DM control was insufficient, microcirculation was worsening only in CC homozygotes.

MMP9 Gene Polymorphism (rs3918242) Increases the Risk of Cardiovascular Disease in Type 2 Diabetes Patients.

Matrix metalloproteinase 9 (MMP-9) C(-1562)T gene polymorphism has been considered a risk factor for cardiovascular disease (CVD). Our study aimed to evaluate the association between this polymorphism and CVD in diabetes patients. The genotyping was performed in 740 patients with T2DM and 400 healthy subjects. A significant difference in the polymorphism distribution was revealed between patients and controls. The T allele and TT homozygote were associated with increased risk of diabetes (OR 1.88, p < 0.0001 and OR 3.77, p = 0.0002, respectively). The comparison between CVD+ and CVD- subgroups showed a much higher frequency of the T allele in patients with CVD (OR 2.87, 95% CI 2.14-3.85, p < 0.0001). Patients with the TT genotype had a higher prevalence of CVD (OR 3.19, 95% CI 1.55-6.56, p = 0.0015). The carrier genotypes (CT/TT) were correlated with HDL levels in both CVD+ and CVD- subgroups (p < 0.001 for both). In the logistic regression analysis, only C(-1562)T SNP was a significant predictor of CVD in diabetic patients (p < 0.001). In conclusion, our study suggests an association between MMP-9 C(-1562)T polymorphism and an increased risk of CVD in T2DM. If replicated in other studies, it could be considered a genetic marker for predicting risk of T2DM and its cardiovascular comorbidity.

A pilot study to examine the association between COX-2 rs5275 polymorphism and the response to repetitive transcranial stimulation in schizophrenia

High frequency (HF)-rTMS has been shown to improve cognitive functions in patients with schizophrenia (SCZ). This study aimed to investigate whether COX-2 rs5275 variants were associated with cognitive improvements following rTMS treatment in patients with SCZ. Forty-eight hospitalized patients with SCZ were assigned to the neuronavigation HF-rTMS group and 28 patients to the sham group over left DLPFC for 1 month. Cognitive function was evaluated using the repeatable battery for the assessment of neuropsychological status (RBANS) at weeks 0 and 4. COX-2 rs5275 polymorphism was genotyped by a technician. At baseline, C allele carriers showed better cognitive performance relative to patients with TT homozygote. Additionally, C allele carriers had greater improvement in memory from the follow-up to baseline following rTMS stimulation, while patients with the TT genotype showed no significant improvement in memory index. More importantly, we found that COX-2 rs5275 was correlated with the response to rTMS after controlling for the covariates. This study data indicate that COX-2 rs5275 was associated with improvements in immediate memory after HF-rTMS treatment in patients with SCZ. rTMS shows an effect on memory only in C allele carriers, but not in those with the TT genotype.

Analysis of polymorphism of innate immunity receptor genes in patients with coronary atherosclerosis and in a population sample from Novosibirsk

Understanding the molecular mechanisms of atherosclerotic vascular lesions formation is necessary both for assessing the risks of cardiovascular diseases and for finding approaches to their therapy. The task remains relevant, despite the large number of studies carried out, because there are differences in the factors of genetic predisposition to atherosclerosis and its complications between different ethno-territorial groups. The aim of this study was to search for genetic variants of pattern recognition receptors associated with lipid metabolism disorders that can lead to the development of coronary atherosclerosis (CA).Material and methods. Analysis of exons and adjacent splicing sites of pattern recognition receptors genes in patients with CA (30 men), and then genotyping of a population sample from Novosibirsk (n = 1441) by real-time PCR for selected rs113706342 of the TLR1 gene and analysis of associations of its carriage with lipid metabolism were performed.Results and discussion. The frequency of the minor allele rs113706342 C of the TLR1 gene in the sample of residents of Novosibirsk was 0.0114 ± 0.0062, the carriage of this variant was associated with an increased level of low-density lipoprotein cholesterol in both women and men (p = 0.009 and p = 0.019, respectively). Women carriers of the minor allele C for rs113706342 also had a statistically significant increase in total serum cholesterol (p = 0.013) compared with TT homozygotes. To test the role of this variant in the development of CA, genotyping of an extended sample of patients is required. In one of the patients with CA, a previously undescribed single nucleotide variant chr16:3614637 G/C was found, leading to the Leu101Val substitution in the NLRC3 gene; segregation analysis is required to assess its functional significance.Conclusions. The association of rs113706342 C of the TLR1 gene with lipid metabolism disorders in the Russian population is shown.

Effects of the SNAP-25 Mnll variant on hippocampal functional connectivity in children with attention deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most widespread and highly heritable neurodevelopmental disorders affecting children worldwide. Although synaptosomal-associated protein 25 (SNAP-25) is a possible gene hypothesized to be associated with working memory deficits in ADHD, little is known about its specific impact on the hippocampus. The goal of the current study was to determine how variations in ADHD's SNAP-25 Mnll polymorphism (rs3746544) affect hippocampal functional connectivity (FC). A total of 88 boys between the ages of 7 and 10 years were recruited for the study, including 60 patients with ADHD and 28 healthy controls (HCs). Data from resting-state functional magnetic resonance imaging (rs-fMRI) and clinical information were acquired and assessed. Two single nucleotide polymorphisms (SNP) in the SNAP-25 gene were genotyped, according to which the study's findings separated ADHD patients into two groups: TT homozygotes (TT = 35) and G-allele carriers (TG = 25). Based on the rs-fMRI data, the FC of the right hippocampus and left frontal gyrus was evaluated using group-based comparisons. The corresponding sensitivities and specificities were assessed. Following comparisons between the patient groups, different hippocampal FCs were identified. When compared to TT patients, children with TG had a lower FC between the right precuneus and the right hippocampus, and a higher FC between the right hippocampus and the left middle frontal gyrus. The fundamental neurological pathways connecting the SNAP-25 Mnll polymorphism with ADHD via the FC of the hippocampus were newly revealed in this study. As a result, the hippocampal FC may further serve as an imaging biomarker for ADHD.

The rs17782313 polymorphism near MC4R gene confers a high risk of obesity and hyperglycemia, while PGC1α rs8192678 polymorphism is weakly correlated with glucometabolic disorder: a systematic review and meta-analysis.

The relationships of the rs17782313 polymorphism near melanocortin 4 receptor gene (MC4R) and the rs8192678 polymorphism in peroxisome proliferator-activated receptor gamma coactivator 1 alpha gene (PGC1α) with metabolic abnormalities have been explored in many populations around the world, but the findings were not all consistent and sometimes even a bit contradictory. Electronic databases including Medline, Scopus, Embase, Web of Science, CNKI and Google Scholar were checked for studies that met the inclusion criteria. Data were carefully extracted from eligible studies. Standardized mean differences (SMDs) were calculated by using a random-effects model to examine the differences in the indexes of obesity, glucometabolic disorder and dyslipidemia between the genotypes of the rs17782313 and rs8192678 polymorphisms. Cochran's Q-statistic test and Begg's test were employed to identify heterogeneity among studies and publication bias, respectively. Fifty studies (58,716 subjects) and 51 studies (18,660 subjects) were respectively included in the pooled meta-analyses for the rs17782313 and rs8192678 polymorphisms. The C-allele carriers of the rs17782313 polymorphism had a higher average level of body mass index (SMD = 0.21 kg/m2, 95% confidence interval [95% CI] = 0.12 to 0.29 kg/m2, p < 0.001), waist circumference (SMD = 0.14cm, 95% CI = 0.06 to 0.23cm, p < 0.001) and blood glucose (SMD = 0.09 mg/dL, 95% CI = 0.02 to 0.16 mg/dL, p = 0.01) than the TT homozygotes. Regarding the rs8192678 polymorphism, no significant associations with the indexes of obesity, glucometabolic disorder and dyslipidemia were detected. However, significant correlations between the rs8192678 polymorphism and multiple glucometabolic indexes were observed in subgroup analyses stratified by sex, age, ethnicity and health status. The meta-analysis demonstrates that the C allele of the MC4R rs17782313 polymorphism confers a higher risk of obesity and hyperglycemia, and the PGC1α rs8192678 polymorphism is weakly correlated with glucometabolic disorder. These findings may partly explain the relationships between these variants and diabetes as well as cardiovascular disease. https://www.crd.york.ac.uk/prospero/, identifier CRD42022373543.

Associations of VEGF Polymorphisms With Retinopathy of Prematurity.

This study investigated the associations between vascular endothelial growth factor (VEGF) polymorphisms and retinopathy of prematurity (ROP) risk. Infants born prematurely at any time from 2009 to 2018 were included. Five single-nucleotide polymorphisms (SNPs) of VEGF were analyzed using real-time PCR in all infants. Multivariate logistic regression was applied to model the associations between VEGF polymorphisms and ROP susceptibility, severity, and premature clinicopathologic characteristics. A total of 334 patients were included and categorized into three groups: those without ROP, those with mild ROP (i.e., ROP not requiring treatment), and those with severe ROP (i.e., ROP for whom treatment was indicated). Among the female patients with ROP, those with VEGF rs3025035 CT (3.231-fold; 95% confidence interval [CI], 1.238-8.431) and a combination of CT and TT genotypes (2.643-fold; 95% CI, 1.056-6.619) exhibited significantly higher risks of severe ROP compared with those with wild-type genotypes. Female ROP infants with VEGF rs3025010 C (TC + CC) alleles had a lower risk of ROP stage ≥3 (odds ratio [OR] = 0.406; 95% CI, 0.165-0.999) than those with TT homozygotes. ROP patients with the VEGF rs10434 A allele (GA + AA) exhibited higher risks of necrotizing enterocolitis (OR = 2.750; 95% CI, 1.119-6.759) and lower risk of bronchopulmonary dysplasia (OR = 0.390; 95% CI, 0.173-0.877) than those with GG homozygotes did. VEGF polymorphisms affect ROP risks differently in male and female infants. In female infants, VEGF rs3025035 with T alleles may predict ROP severity, and VEGF rs3025010 with C alleles may protect against severe ROP.

Post-Traumatic Stress Disorder Is Associated with Elevated Plasma Cholesterol in Female TT Homozygotes of LDLR rs5925.

To explore the mechanism of inconsistent relationships between plasma lipid profiles and post-traumatic stress disorder (PTSD) reported before, we hypothesized that interplays might exist between PTSD and a variation of rs5925 at low-density lipoprotein receptor (LDLR) gene on plasma lipid profiles. To test our hypothesis, we analyzed the plasma lipid profiles of 709 high school pupils with various genotypes of LDLR rs5925 and with or without PTSD. The results demonstrated that PTSD prevalence in the C allele carriers was higher than that in the TT homozygotes regardless of gender. The C allele carriers had higher levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), ratios of TC to high-density lipoprotein cholesterol (TC/HDL-C) and LDL-C/HDL-C than the TT homozygotes in the male controls, and only higher TC in the female controls, but no differences in the male or female PTSD subjects. PTSD increased TC in the female TT homozygotes but not in the female C allele carriers. PTSD increased TC/HDL-C in the male TT homozygotes but not in the C allele carriers. These results suggest interactions between PTSD and LDLR rs5925 on plasma lipid profiles, which may be among the explanations for previously reported inconsistent relationships between LDLR rs5925 or PTSD and plasma lipid profiles, and facilitate the development of precision medicine interferences in hypercholesterolemia in individuals with different genetic backgrounds and psychiatric status. Psychiatric care or drug supplement may particularly be needed by female hypercholesterolemic subjects with the TT genotype of LDLR rs5925 in Chinese adolescents.

Association between DRD2/ANKK1 rs1800497 C > T polymorphism and post-traumatic stress disorder susceptibility: a multivariate meta-analysis.

Previous studies have suggested that the DRD2/ANKK1 rs1800497 C > T polymorphism plays a critical role in the risk of post-traumatic stress disorder (PTSD). However, published data are inconsistent or even contradictory. Therefore, we conducted a meta-analysis to explore the underlying correlation between the rs1800497 C > T polymorphism and PTSD risk. A total of five online databases were searched, and all related studies were reviewed up to 1 October 2022. Critical information was extracted, and quality assessment was conducted for all included studies. Multivariate meta-analyses were performed for the genetic model choice, and the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to examine the statistical power of the genetic models. In addition, heterogeneity, sensitivity, cumulative analysis, and publication bias were analyzed to guarantee statistical power. Overall, 12 observational studies involving 5,515 subjects were included and analyzed in this meta-analysis. Multivariate analysis indicated that a co-dominant genetic model was most likely the best choice. Pooled results revealed an elevated PTSD risk in mutated homozygote TT carriers in the general population (TT vs. CC: OR = 1.73, 95% CI = 1.14-2.62, P = 0.01, I2 = 58.9%) and other specific subgroups. Moreover, similar results were observed in other genetic models using univariate analysis. Current evidence suggests that the DRD2/ANKK1 rs1800497 C > T polymorphism may contribute to PTSD susceptibility.

The genetic susceptibility analysis of TAAR1 rs8192620 to methamphetamine and heroin abuse and its role in impulsivity.

Abnormal genetic polymorphism of trace amine-associated receptor 1 (TAAR1) rs8192620 site has been confirmed to induce methamphetamine (MA) use and drug craving. However, the genetic susceptibility difference between MA addicts and heroin addicts is unknown. This study evaluated genetic heterogeneity of TAAR1 rs8192620 between MA and heroin addicts and elucidated whether rs8192620 genotypes associated with discrepancy in emotional impulsivity, which would help to instruct individualized treatment in addiction via acting on TAAR1 and evaluate risk of varied drug addiction. Participants consisting of gender-matched 63 MA and 71 heroin abusers were enrolled in the study. Due to mixed drug usage in some MA addicts, MA users were further subdivided into 41 only-MA (only MA taking) and 22 mixed-drug (Magu composed of about 20% MA and 70% caffeine) abusers. Via inter-individual single nucleotide polymorphism (SNP) analysis and two-sample t tests, respectively, the genotypic and Barratt Impulsiveness Scale-11 (BIS-11) scores differences between groups were completed. With following genotypic stratification, the differences in BIS-11 scores between groups were analyzed through two-sample t test. Individual SNP analysis showed significant differences in alleles distribution of rs8192620 between MA and heroin subjects (p = 0.019), even after Bonferroni correction. The TT homozygotes of rs8192620 dominated in MA participants, while C-containing genotypes in heroin (p = 0.026). There was no association of genotypes of TAAR1 rs8192620 with addicts' impulsivity. Our research indicates that the TAAR1 gene polymorphism might mediate the susceptibility discrepancy between MA and heroin abuse.