Association of 5-HTTLPR Serotonin Transporter Gene Polymorphism and Val66Met Brain-Derived Neurotrophic Factor Gene Polymorphism with Auditory N100 Evoked Potential Amplitude in Patients with Endogenous Psychoses

We studied the relationship between genes of serotonin transporter and brain-derived neurotrophic factor and parameters of AEP N100 wave to a non-significant stimulus in patients with endogenous mental diseases. In patients with endogenous psychoses, a significant effect of BDNF Val66Met marker on N100 wave amplitude was revealed: the mean N100 amplitude was higher in carriers of Val/Val genotype compared to Val/Met genotype carriers. The effect of the 5-HTTLPR marker on the wave amplitude was less pronounced (tendency): the SS genotype was associated with higher N100 amplitude. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 146, No. 11, pp. 541–544, November, 2008     

Association between HLA-G 14bp Gene Polymorphism and Serum sHLA-G Protein Concentrations in Preeclamptic Patients and Normal Pregnant Women

Background: Preeclampsia (PE) is a multisystem syndrome that is a primary source of fetal–maternal morbidity and mortality. Human leukocyte antigen-G (HLA-G) is a nonclassical Major histocompatibility complex (MHC) class-Ib molecule expressed on the extravillous trophoblast and seems to have immunomodulatory functions during pregnancy. The purpose of our study was to investigate whether HLA-G may be a vital marker in the modulation of the pregnancy.

Methods: In this case-control study, a number of 150 healthy pregnant women and 150 patients with PE had been genotyped for the 14 base-pair (bp) insertion/deletion polymorphism in exon 8 of the HLA-G gene, and the serum level of soluble HLA-G (sHLA-G) protein was measured using the enzyme-linked immunosorbent assay.

Results: Data showed that the PE syndrome was not related to the HLA-G 14 bp genotype. But, the serum level of sHLA-G in PE patients was significantly lower than that in healthy pregnant women in the third trimester (11.74 and 24.48 U/ml, respectively, p < 0.001). However, no significant association was observed between the HLA-G 14 bp genotype and serum sHLA-G level.

Conclusion: Our results demonstrate that measurement of sHLA-G protein level may be helpful as a primary diagnosis for the pathogenesis of PE. Overall, this study suggests that the association between HLA-G 14 bp polymorphism and serum sHLA-G level in different ethnic populations of PE should be taken into consideration.     

Meta-analysis of Association Between a Catechol-O-Methyltransferase Gene Polymorphism and Attention Deficit Hyperactivity Disorder

There have been conflicting reports on the association between the Val158/108Met polymorphism of the catechol-O-methyltransferase (COMT) gene and attention deficit hyperactivity disorder (ADHD). Therefore we would like to perform a meta-analysis of previous studies to assess the overall magnitude and significance of the association. Family-based and case–control studies of the association between the COMT gene polymorphism and ADHD were searched systematically and comprehensively. Odds ratios (OR) of association were pooled by the fixed effects model if no significant heterogeneity was present among different studies. Subgroup analysis by gender and ADHD subtypes were also performed. Eleven family-based and two case–control studies were identified. After pooling the results, no significant association between the COMT Val158/108Met polymorphism and ADHD was found (OR 0.99 (95% CI: 0.88–1.12), P = 0.87). There was also no significant association when the results were stratified by gender or ADHD subtype. There was no significant statistical heterogeneity (χ² = 12.27, P = 0.2) although clinical heterogeneity was present in the studies, especially the ethnicity of subjects. Sensitivity analysis demonstrated absence of undue influence of any single study. Standard regression analysis showed no significant publication bias. We concluded that no significant association was present between the most common COMT gene polymorphism and ADHD. Further studies should employ larger sample size in more homogeneous subjects. Further investigations in moderator variables and gene–gene and gene–environment interactions are also warranted.     

The STin2VNTR Polymorphism of the Serotonin Transporter Protein: Association with the Efficiency of Short-Term Memory in Young and Elderly Subjects

Neuroscience and Behavioral Physiology - Cognitive abilities and the rate of their extinction with age are shown to be determined to a significant extent by genetic factors. The serotoninergic...     

Association of -717A>G Polymorphism in the C-Reactive Protein Gene (CRP) with Schizotypal Personality Traits

Bulletin of Experimental Biology and Medicine - Associations between schizotypal traits and genes coding for inflammation markers (Creactive protein and TNF-α) were studied in 222 healthy men...     

The Course and Outcomes of Episodic Endogenous Psychoses with Juvenile Onset (a follow-up study)

A clinical follow-up study (mean follow-up period 16.8 ± 6.4 years) of 278 patients with juvenile-onset endogenous episodic psychosis (Endogenous Psychosis Episodic Type, EPET – ICD-10 F20.03, F20.23, F25) with first episodes in 1984–1995 was performed. The period of the most intense occurrence of repeated episodes occurred during the first five years from the initial episode (almost all repeat episodes in the patients occurred during this period). At the time of the follow-up study, “good” outcomes were seen in 18.7% of patients, “relatively good” in 33.8%, “relatively poor” in 30.2%, and “poor” in 17.2%. Analysis of correlations between disease course and outcome and types of manifest episode and a number of clinicalpathogenetic parameters yielded several statistically significant criteria for clinical and social prognosis. Nosological evaluation at the time of the follow-up study showed that 76.2% of patients had schizophrenia (episodic progressive in 61.1%, recurrent in 15.1%) and 28.3% had schizoaffective psychosis. Comparison of the data with results from previous analogous studies led to the conclusion that the contemporary pathomorphosis of EPET is more favorable, with trends to improvements in disease course and outcome, decreases in progression, and significant reductions in cases of transition to a chronic course.     

Endogenous and Exogenous Attention in Patients with Conversion Paresis

Endogenous and exogenous attention of patients with conversion paresis was investigated using Posner's ‘covert orienting of visual attention’ task. In the light of previous evidence showing that inhibition of higher‐level control functions plays a role in conversion paralysis (e.g., Marshall, Halligan, Fink, Wade, & Frackowiak, 1997), patients were expected to display weaker cue effects in the endogenous condition and weaker inhibition of return (IOR) in the exogenous condition. Eight patients with conversion paresis in one or more limbs and eight healthy controls were administered the attention task in a verbal response condition and in a limb response condition in which subjects responded with each limb separately. When responding verbally, patients showed relatively weakened endogenous cue effects on a 150‐ms stimulus onset asynchronicity (SOA) and no IOR in the exogenous condition. Comparable effects emerged when patients responded with affected limbs but not when they responded with unaffected limbs. The findings suggest impairment in voluntary attention. High‐level inhibition is suggested to interfere with the orientation to stimuli that prime responses with affected limbs. The fact that similar results were found for verbal responses is interpreted as supporting the view that attention deficits are manifested on a high, abstract level of cognitive processing.     

Association between the Catechol-O-Methyltransferase (COMT) Val158Met Polymorphism and Alexithymia in Patients with Obsessive-Compulsive Disorder

PurposeAlexithymia, defined as a deficit in the ability to recognize and describe one''s own feelings, may be related to the development and maintenance of obsessive-compulsive symptoms. The aim of this study was to evaluate the association between the catechol-O-methyltransferase (COMT) Val¹⁵⁸Met polymorphism and alexithymia in patients with obsessive-compulsive disorder (OCD).ResultsPatients with the COMT Val/Val genotype had significantly higher total and "difficulty identifying feelings" (DIF) subdimension scores than those with the Val/Met or Met/Met genotypes. Patients with the COMT Val/Val genotype had significantly higher "difficulty describing feelings" (DDF) subdimension scores than those with the COMT Val/Met genotype. However, there were no differences in the scores for the "externally oriented thinking" (EOT) subdimension among the three genotypes.ConclusionThese results indicate that the high-activity Val allele of the COMT Val¹⁵⁸Met polymorphism is associated with increased alexithymic traits in patients with OCD. The present finding suggests that alexithymia is an endophenotype of OCD that is mediated by the COMT Val¹⁵⁸Met polymorphism.     

IL12 Gene Polymorphism in Association with Hepatocellular Carcinoma in HCV-infected Egyptian Patients

Background: Hepatocellular carcinoma has been recorded the commonest cancer in Egypt. This increasing incidence may be attributed to the high prevalence of hepatitis C virus with its complications, so this study aimed to investigate the association between the potentially functional polymorphisms of IL12A and IL12B genes as a risk factor of development of hepatocellular carcinoma (HCC) on top of hepatitis C virus (HCV) infection in an Egyptian population.

Materials and methods: We genotyped two loci of IL12 which were rs568408 (3’UTR G>A) for IL12A and rs3212227 (3’UTR A>C) for IL12B in 78 patients with HCC on top of chronic HCV infection. In addition, 64 cancer-free chronic HCV patients were studied, besides 92 healthy subjects who were included as control.

Results: Study of rs568408 (G>A) gene polymorphism showed that the A allele is higher while the G allele is lower in HCC cases than cancer-free chronic HCV patients (p = 0.006*). The A-containing genotypes AG and (AG+AA) were higher while the GG was lower (p = 0.009* and p = 0.005*), respectively. The study of the rs3212227 (A>C) polymorphism showed neither statistically significant differences between the C and A allele (p = 0.2) nor between CC, AC, or AC+CC in HCC cases and cancer-free chronic HCV patients (p = 0.7, p = 0.2, and p = 0.29), respectively.

Conclusion: Our findings showed that IL12A rs568408 (G>A) polymorphism may contribute to the risk of HCC on top of chronic HCV infection, whereas that of IL12B rs3212227 (A>C) do not.     

Possible Association of the Human KCNE1 (minK) Gene and QT Interval in Healthy Subjects: Evidence from Association and Linkage Analyses in Israeli Families

QT interval prolongation is associated with increased risk of sudden and non‐sudden cardiac death. Potassium channel gene variants are associated with inherited long QT syndromes. Using linkage and association analyses, we investigated whether variants in the potassium channel subunit KCNE1 are associated with QTc intervals in an unselected population sample of 80 kindreds living in kibbutz settlements in Israel. Variance‐component linkage analysis revealed weak evidence of linkage of KCNE1 polymorphisms with QTc intervals. Family‐based association analysis showed a significant association between the G38S polymorphism and QTc interval. Further quantitative trait association analysis demonstrated a significant residual heritability component (h²= 0.33), and that the effect of the G38S variant allele is modified by gender. Estimated maximum likelihood parameters from these models indicated that male gender, age, hypertension, diabetes, hypercholesterolemia, fibrinogen and BMI were positively associated with QTc interval; level of education and cigarette smoking showed an inverse association. Both erythrocyte membrane n‐6 and n‐3 fatty acids showed a significant inverse association with QTc interval. While more than 15.8% of QTc variability was contributed by covariates, another 4.7% was explained by dietary factors, the G38S polymorphism explained 2.2%, and approximately 36% was explained by polygenes. An in silico analysis showed also that the novel V80 SNP, another KCNE1 synonymous variant, abolishes the recognition for a splicing enhancer, which may lead to an increased effect of the G38S mutation. These results demonstrate that, in addition to polygenic background, dietary factors and other covariables, the KCNE1 G38S variant is involved in determining QTc levels in this population‐based sample of families.     

Association of Serotonin Transporter Promoter Gene Polymorphism (5-HTTLPR) With Depression in Costa Rican Schizophrenic Patients

Abstract:

Depression and suicidal behavior are frequently observed in patients with schizophrenia. The serotonin transporter protein regulates serotonergic signaling at synapses and is encoded by a single gene (SLC6A4; Locus Link ID: 6532), located at 17q11.1-q12 with two polymorphic variants (the short and the long allele). The short allele of serotonin transporter gene has been associated with depression and suicidality in individuals who suffered negative life events and with depression in individuals with chronic psychosis.. Subjects were recruited from a genetic study of schizophrenia conducted in Costa Rica. The authors replicated their previous research, using a more narrow phenotype (only schizophrenic subjects) and a more ethnically homogenous sample (only Costa Rican schizophrenic individuals who were not included in the previous study). The authors hypothesized that subjects with at least one copy of the serotonin transporter promoter gene polymorphism (5-HTTLPR) “s” allele would have a greater history of lifetime depression and suicidability rate than those who had an “l/l” genotype. The authors analyzed 155 subjects with a DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) diagnosis of schizophrenia (73% male, age at interview 38.3, SD = 11.23). The genotype distribution was “ss” 58 (37%), “sl” 69 (45%), and “ll” 28 (18%). In the secondary analysis, the authors explored association of the “s” allele with lifetime history of suicide behavior in 173 subjects (18 more subjects than primary analysis because schizophrenic individuals were included regardless of history of depression). The authors found that subjects carrying at least one short allele had a significant increased lifetime risk for depressive syndromes (χ² = 5.4, df = 1, P = 0.02; odds ratio [OR] = 2.7, 95% confidence interval [CI] = 1.15–6.3). No association was found for suicidal behavior in the same sample (χ² = 0.928, P = 0.629). In conclusion, the genotype at the 5-HTTLPR promoter polymorphic locus increases the risk of developing major depression but not suicidal behavior during the course of the schizophrenia in these patients. Due to the small sample size, these results should be followed by definitive replication.     

干扰素诱导跨膜蛋白3基因多态性与小儿流感严重程度相关性研究

目的分析轻症和重症流感患儿干扰素诱导跨膜蛋白3基因(IFITM3)rs12252T/C基因多态性的分布特点,探讨其基因多态性与小儿流感严重程度的相关性。方法选择符合流感诊断标准的患儿60例,其中重症流感患儿和轻症流感患儿各30例,通过从患儿外周血提取DNA扩增相应的目的片段并测序,检测IFITM3基因rs12252单核苷酸多态性分布情况,统计学分析小儿流感遗传易感性、严重程度相关的基因型和等位基因。结果 IFITM3基因rs12252 CC基因型在重症组患儿中占70.00%而在轻症组仅占26.67%;在隐形遗传模型中,CC纯合子比TT纯合子和CT杂合子有6倍大的风险患重症流感(OR=6.42,95%CI为2.08~19.76)。结论 IFITM3基因rs12252T/C基因多态性对中国人群流感的流行病学具有重要影响,CC基因型可能与儿童流感的严重程度相关。     

Association of E-selectin Gene Polymorphism (S128R) with Ischemic Stroke and Stroke Subtypes

E-selectin is an important inflammatory cytokine involved in the pathogenesis of various diseases such as atherosclerosis and stroke. We investigated the association of E-selectin gene polymorphism (S128R) with ischemic stroke and its subtypes. We studied 610 patients with ischemic stroke and 610 age- and sex-matched healthy controls. The ischemic stroke was classified according to Trial of Org10172 in Acute Stroke Treatment (TOAST). E-selectin gene polymorphism (S128R) was determined by polymerase chain reaction–restriction fragment length polymorphism technique. We found statistically significant difference in the genotypic distribution between patients and controls (for AC vs. AA, χ ²?=?49.5; p?<?0.001, odds ratio?=?5.47(95 % CI, 3.25–9.21). A significant difference was observed in the frequency of C and A alleles in patients and controls (for C vs. A, χ ²?=?47.4; p?<?0.001, odds ratio?=?5.13 (95 % CI, 3.06–8.57). Multiple logistic regression analysis revealed that the most predictive risk factor for stroke was AC genotype (adjusted odds ratio?=?1.450 (95 % CI, 1.23–2.75) and p?=?0.001), hypertension, smoking, and diabetes (p?=?0.001 in each case). We also found a significant association of AC genotype with intracranial large artery atherosclerosis (p?<?0.01, odds ratio?=?9.37, (95 % CI, 5.31–16.5) and small artery occlusion (p?<?0.0001, odds ratio?=?9.81 (95 % CI, 4.94–19.4). Our results indicate that the individuals bearing AC genotype of E-selectin gene polymorphism (S128R) are more prone to stroke than AA genotype.     

Association between a TGFBR2 Gene Polymorphism (rs2228048, Asn389Asn) and Acute Rejection in Korean Kidney Transplantation Recipients

Transforming growth factor-β (TGF-β) signaling transduction initiates TGF-β activation, resulting in activation of TGF-β receptor II (TGFBR2). Any quantitative and qualitative changes in TGFBR2 are expected to affect the TGF-β signaling pathway, which occupies a central position with respect to the regulation of cell growth, differentiation, apoptosis, immune reaction, angiogenesis and extracellular matrix formation. Recent studies have shown that TGF-β1 gene polymorphisms may confer susceptibility to early acute and chronic allograft rejection in kidney transplantation recipients. In this study, we assessed whether polymorphisms of the TGFBR2 gene were associated with susceptibility to kidney transplantation rejection. A total of 347 renal allograft recipients transplanted at three centers in Korea were analyzed. Three SNPs (rs764522, rs3087465, rs2228048) of the TGFBR2 gene were genotyped from genomic DNA with direct sequencing. Multiple logistic regression models (codominant, dominant, recessive, and log-additive) were performed to evaluate odds ratios (ORs), 95% confidence intervals (CIs), and p-values. A total of 63 patients (18%) developed acute rejection (AR). There were no significant differences in age, sex, number of HLA mismatches, cause of renal failure, or immunosuppressant regimen between the AR and non-AR group. The synonymous SNP rs2228048 was significantly associated with AR (p = 0.020 in recessive model, and p = 0.036 in log-additive model. The allele frequencies of rs2228048 were different between the AR and non-AR group (p = 0.026). These results suggest that the synonymous TGFBR2 gene SNP rs2228048 may be associated with the development of AR in Korean kidney transplantation recipients.     

Family Based Association Analyses between the Serotonin Transporter Gene Polymorphism (5-HTTLPR) and Neuroticism,Anxiety and Depression

We studied the association between the short/long promotor-based length polymorphism of the serotonin transporter gene (5-HTTLPR) and neuroticism, anxiety and depression. Subjects included twins, their siblings and parents from the Netherlands Twin Register (559 parents and 1,245 offspring). Subjects had participated between one and five times in a survey study measuring neuroticism, anxiety and depression. Offspring of these families were also approached to participate in a psychiatric interview diagnosing DSM-IV major depression. Within-family and total association between 5-HTTLPR and these traits were tested. Only three of the 36 tests showed a significant effect of 5-HTTLPR (P < 0.05). These effects were in opposite directions, i.e. both negative and positive regression coefficients were found for the s allele. No additive effect of the s allele was found for DSM-IV depression. Our results strongly suggest that there is no straightforward association between 5-HTTLPR and neuroticism, anxiety and depression. Edited by Stacey Cherny