Association of the 54-nucleotide repeat polymorphism of hPer3 with heroin dependence in Han Chinese population

Circadian clock genes have the function of producing circadian rhythm. They are also implicated in the origin or development of many diseases such as cancers and neuropsychiatric diseases. The purpose of this study is to determine whether the 54-nucleotide repeat polymorphism of hPer3 , one of the circadian clock genes, associates with heroin dependence. DNA samples were obtained from 209 Chinese heroin-dependent subjects and 249 Chinese healthy controls. The 54-nucleotide repeat polymorphism was detected by polymerase chain reaction and DNA agarose gel electrophoresis. The frequency of four-repeat allele was significantly higher ( χ ²= 10.64, P = 0.001; corrected for multiple tests, P = 0.003) in the mixed gender heroin-dependent subject group (four repeat: 0.89, five repeat: 0.11) than in the mixed gender control group (four repeat: 0.81, five repeat: 0.19); the frequency of four-repeat allele was also significantly higher ( χ ²= 10.00, P = 0.002; corrected for multiple tests, P = 0.006) in the male heroin-dependent subject group (four repeat: 0.89, five repeat: 0.11) than in the male control group (four repeat: 0.81, five repeat: 0.19); for females, no significant trend was observed with the 54-nucleotide repeat polymorphism between the heroin-dependent subject group and the control group. Our results suggest that the 54-nucleotide repeat polymorphism of hPer3 significantly associates with heroin dependence at the allele frequency level and may be a potential risk factor for the development of heroin dependence.     

Human diurnal preference and circadian rhythmicity are not associated with the CLOCK 3111C/T gene polymorphism

Genetic association studies of the CLOCK 3111C/T polymorphism and diurnal preference have yielded conflicting results since the first report that the 3111C allele was associated with eveningness. The goal of the present study was to investigate the association of this polymorphism with diurnal preference and circadian physiology in a group of 179 individuals, by comparing the frequency of the 3111C allele to diurnal preference, habitual sleep timing, circadian phase markers, and circadian period. We did not find a significant association between this allele and morningness/eveningness or any circadian marker.     

Association of T3111C polymorphism in 3'-untranslated region of the CLOCK gene with the risk of essential arterial hypertension and coronary artery disease in the Russian population Karelia

Allele and genotype distributions of the T3111C polymorphism in 3'-untranslated region of the CLOCKgene were examined in the groups of Russian patients with essential arterial hypertension (EAH) and coronary artery disease (CAD), and in control group of Russia residents of the Republic of Karelia. The genotype frequency distributions of the polymorphism examined in the EAH and CAD patients were statistically significantly different from that in the individuals without clinical signs of these diseases. The CC genotype frequency in EAH and CAD males was higher, and in the corresponding females it was lower than in males and females from the control group. Male CC carriers were characterized by a possible increased risk of EAH: OR (95% CI) = 1.42 (0.56; 3.58). Moreover, the presence of the CC genotype in males could increase the risk of CAD: OR (95% CI) = 1.58 (0.63; 3.93).     

The CLOCK 3111T/C single nucleotide polymorphism and daytime fluctuations of gastric motility in healthy young women: A preliminary study

The 3111T/C single nucleotide polymorphism (SNP) of Circadian Locomotor Output Cycles Kaput (CLOCK) gene reportedly affects gastric motility before breakfast. It is of interest to know whether this SNP can affect the motility during the daytime. We investigated the association between the CLOCK 3111T/C SNP and several gastric motility parameters during the time period from 8:00 to 20:00 in 34 young women with scheduled meals. There were similar daytime fluctuations in gastric motility before and after the meals between the major (T/T) and minor (T/C) allele carriers. The CLOCK SNP may affect daytime gastric motility less than food stimulation.     

Lipid peroxidation depends on the clock 3111T/C gene polymorphism in menopausal women with Insomnia

ABSTRACT

A comparative analysis of lipid peroxidation processes and antioxidant defense system in Caucasian menopausal women with/without insomnia depending on the genotype of Clock 3111T/C gene polymorphism was performed. Two hundred and fourteen Caucasian menopausal women divided into control (without insomnia) and main group (with insomnia) were examined. Lipid peroxidation (conjugated dienes, thiobarbituric acid reactants) and antioxidant defense system parameters (?-tocopherol, retinol, reduced and oxidized glutathione, glutathione S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase) were determined by spectrofluorophotometer and immunoenzymometric methods. Patients with insomnia carriers of the TT-genotype had a significantly higher thiobarbituric acid reactants level and glutathione peroxidase activity as compared to group with insomnia carriers of the minor 3111C-allele (p < .05). A comparative analysis of the parameters in the women of the main and control groups showed higher conjugated dienes, thiobarbituric acid reactants levels and lower retinol, reduced glutathione levels, glutathione reductase activity in women with insomnia carriers of the TT-genotype (p < .05). The carriers of the minor allele with insomnia had a higher conjugated dienes levels and lower glutathione peroxidase activity as compared to control (p < .05). Thus, lipid peroxidation and antioxidant system parameters in Caucasian menopausal women with insomnia depend on the Clock 3111T/C gene polymorphism.     

Association of the melatonin circadian rhythms with clock 3111T/C gene polymorphism in Caucasian and Asian menopausal women with insomnia

A comparative analysis of melatonin circadian rhythms in Caucasian (incoming population) and Asian (indigenous population) menopausal women with/without sleep disorders depending on the genotype of Clock 3111T/C gene polymorphism was realized.The melatonin level in the saliva was determined four times a day (6:00–7:00, 12:00–13:00, 18:00–19:00, 23:00–00:00 h). The Caucasian women—carriers of the TT-genotype with insomnia as compared to control group—had a higher morning melatonin level and a lower night melatonin level. The Asian women with TT-genotype and insomnia had a lower levels of melatonin as compared to control at daytime, evening and night. A significantly higher melatonin level in the early morning hours was detected in the Caucasian women—carriers of the TT-genotype with insomnia as compared to group womencarriers of the minor 3111C-allele. There were no statistically significant differences in the circadian rhythms of melatonin in the Asian women depending on the genotype of the Clock 3111T/C polymorphism. An assumption with respect to the protective role of the minor allele 3111C in the development of insomnia associated with the displacement of melatonin circadian rhythms in the representatives of the incoming population was made.     

The 3111T/C polymorphism interacts with stressful life events to influence patterns of sleep in females

Genetic variations in clock-relevant genes have been investigated in relation to sleep abnormalities, both in healthy populations and in mood-disorder patients with inconsistent results. Environmental influences may moderate associations between genes and phenotype. The authors examined the CLOCK 3111T/C polymorphism and several variants within the PER3 gene and their possible interaction with stressful life events in a group of female volunteers (n = 415). Gene-environment (G × E) interactions and gene main effects were investigated on depressive symptoms using the Beck Depression Inventory and on change of sleep patterns (Item 16). Results showed a G × E interaction on alteration of sleeping pattern: the 3111C homozygous genotype reported greater disruption in sleep pattern after the experience of stressful life events. Within the PER3 gene, one G × E interaction was observed with rs228642 on sleep change. These findings show that the 3111T/C polymorphism is not associated with depressive symptoms, but only with symptoms of sleep change in the case of prior stressful life experiences. The combination of a sensitive genotype (3111C/C) and environmental stress increases vulnerability to circadian rhythm disruption in females.     

Association of GNB3 gene C825T polymorphism with coronary heart disease

The C825T polymorphism in the gene encoding the G protein beta 3 subunit (GNB3) causes enhanced G protein activation and the increased in vitro cell proliferation. We investigated the association of gene GNB3 C825T polymorphism with coronary artery disease (CAD) in the Russian population. A total of 313 patients with CAD diagnosed on the basis of clinical studies and coronary angyography were examined. The control group included 132 individuals that lacked clinical CAD symptoms and had matching profile of coronary artery disease risk factors. Blood pressure was measured using standard protocols. Increased levels of diastolic and systolic pressure was observed in both groups. The allele and genotype frequencies of this polimorphic marker were significantly higher in the CAD patients than in control. We found that the frequency of allele C and genotype CC was significantly higher in the CAD patients (OR = 1.55; P = 0.0079; OR = 1.63; P = 0.0215, respectively), which suggests higher risk of this pathology in carriers of allele C and genotype CC. Thus, in the Russian population coronary artery disease is associated with GNB3 allele C and genotype CC.     

Association of GNB3 gene C825T polymorphism with coronary heart disease

The C825T polymorphism in the gene encoding the G protein beta 3 subunit (GNB3) causes enhanced G protein activation and the increased in vitro cell proliferation. We investigated the association of gene GNB3 C825T polymorphism with coronary artery disease (CAD) in the Russian population. A total of 313 patients with CAD diagnosed on the basis of clinical studies and coronary angyography were examined. The control group included 132 individuals that lacked clinical CAD symptoms and had matching profile of coronary artery disease risk factors. Blood pressure was measured using standard protocols. Increased levels of diastolic and systolic pressure was observed in both groups. The allele and genotype frequencies of this polimorphic marker were significantly higher in the CAD patients than in control. We found that the frequency of allele C and gen-. otype CC was significantly higher in the CAD patients (OR = 1.55; P = 0.0079; OR = 1.63; P = 0.0215, respectively), which suggests higher risk of this pathology in carriers of allele C and genotype CC. Thus, in the Russian population coronary artery disease is associated with GNB3 allele C and genotype CC.     

The association of a cystatin C gene polymorphism with late-onset Alzheimer's disease and vascular dementia

A polymorphism in the cystatin C (CST3) gene was suggested to associate with Alzheimer's disease (AD). In the present study we attempted to determine the association between CST3 polymorphism and AD or vascular dementia (VD), and whether such effects are dependent of the APOE4 allele. The polymorphisms of CST3 genotype were determined using polymerase chain reactions (PCR) followed by gel electrophoresis in 124 AD, 70 VD, and 115 control individuals. No statistical difference in CST3B allele frequencies was observed among all three groups. Associations between CST3B/B genotype and AD patients older than 75-year-old, or VD patients younger than 75-year-old were evident. The APOE4 allele alone significantly increased the odds for the developing AD, but not VD. A logistic regression analysis revealed that either CST3 or its interaction with APOE4 were not significant predictors of AD. However, a synergistic association of CST3 and APOE4 alleles was observed in predicting VD patients. These results suggest that CST3 might interact with APOE4 on conferring vascular pathologies.     

G-protein beta3 subunit gene C825T polymorphism in patients with vesico-ureteric reflux

The C825T polymorphism in the GNB3 gene encoding a beta3 subunit from heterotrimeric G-proteins correlates strongly with the variation in activity of the G-proteins. It has so far been associated with a variety of medical conditions, but has not been tested for association with vesico-ureteric reflux (VUR). Primary VUR is a condition of genetic origin that appears to be inherited in an autosomal dominant mode, but with reduced penetrance. The constitutional change in G-protein-mediated cell signaling associated with the C825T polymorphism might be one of the factors that participate in the development of VUR by modifying the effect of still unknown mutated gene(s). A significant difference in genotype frequencies (chi(2) = 7.38, P = 0.025, df = 2) was observed between patients with primary VUR (33 CC homozygotes, 40 CT heterozygotes, 12 TT homozygotes) and healthy controls with no medical record of reflux (114 CC homozygotes, 88 CT heterozygotes, 18 TT homozygotes). This result suggests that the C825T polymorphism of the GNB3 gene might be associated with the development of VUR.     

Systematic polymorphism analysis of the CYP2C9 gene in Chinese Han and Tibetan populations

Study about polymorphism of the CYP2C9 was not reported in the Chinese Tibetan population and there was no comparison of genetic polymorphism pattern of CYP2C9 between Chinese Han and Tibetan populations. Here we screened the genetic polymorphisms of functional regions of the CYP2C9 in 100 unrelated healthy Chinese Han and Tibetan volunteers, respectively, using direct sequencing. A total of 20 variants were detected and there were different distribution of allelic and genotype frequencies, linkage disequilibrium patterns, haplotype structures and htSNPs between the two populations. CYP2C9*3 is a major functional variant of CYP2C9 in the two populations and *11 allele was only detected in Tibetan population. The determined genetic information of CYP2C9 in Chinese Han and Tibetan populations might serve as a baseline for larger studies on determining metabolic phenotypes of CYP2C9 substrate drugs and also provide important data for the advance of personalized medicine in Chinese Han and Tibetan populations.     

Association of BDNF gene polymorphism with bipolar disorders in Han Chinese population

Recent data suggest that brain‐derived neurotrophic factor (BDNF) plays an essential role in neuronal plasticity and etiology of bipolar disorders (BPD). However, results from different studies have been inconsistent. In present study, 342 patients who met DSM‐IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) criteria for bipolar disorders type I (BPD‐I) or type II (BPD‐II) and 386 matched health controls were enrolled, and TaqMan® SNP Genotyping Assays (Applied Biosystems, Foster City, CA, USA) were applied to detect the functional polymorphism rs6265 (Val66Met) of BDNF gene. Treatment response to lithium and valproate was retrospectively determined. The association between Val66Met polymorphism and BPD, treatment response to mood stabilizers, was estimated. The genotype and allele distribution of Val66Met polymorphism between BPD patients and control subjects showed significant difference (genotype: χ² = 6.18, df = 2, P = 0.046; allele: χ² = 5.01, df = 1, P = 0.025) with Met allele as risk factor for disease susceptibility (OR = 0.79, 95%CI as 0.64–0.97). The post hoc analysis interestingly showed that Met allele had opposite effect on the treatment response for BPD‐I and BPD‐II separately. For BPD‐I patients, the response score in Val/Val group was significantly lower than that in Met allele carriers (t = ?2.27, df = 144, P = 0.025); for BPD‐II patients, the response score in Val/Val group was significantly higher than that in Met allele carriers (t = 2.33, df = 26, P = 0.028). Although these results should be interpreted with caution because of the limited sample for Val/Val genotype in BPD‐II patients (N = 5), these findings strengthen the hypothesis that BDNF pathway gets involved in the etiology and pharmacology of BPD and suggest the differences between BPD‐I and BPD‐II.     

Relationship of an hRAD54 gene polymorphism (2290 C/T) in an Ecuadorian population with chronic myelogenous leukemia

The hRAD54 gene is a key member of the RAD52 epistasis group involved in repair of double-strand breaks (DSB) by homologous recombination (HR). Thus, alterations of the normal function of these genes could generate genetic instability, shifting the normal process of the cell cycle, leading the cells to develop into cancer. In this work we analyzed exon 18 of the hRAD54 gene, which has been previously reported by our group to carry a silent polymorphism, 2290 C/T (Ala730Ala), associated to meningiomas. We performed a PCR-SSCP method to detect the polymorphism in 239 samples including leukemia and normal control population. The results revealed that the 2290 C/T polymorphism has frequencies of 0.1 for the leukemia and 0.1 for the control group. These frequencies show no statistical differences. Additionally, we dissected the leukemia group in chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL) to evaluate the polymorphism. The frequencies found in these subgroups were 0.14 for CML and 0.05 for ALL. We found statistically significant differences between CML patients and the control group (p < 0.05) but we did not find significant differences between ALL and the control group (p > 0.05). These results suggest a possible link between the 2290 C/T polymorphism of the hRAD54 gene and CML.     

Association of the D repeat polymorphism in the ASPN gene with developmental dysplasia of the hip: a case-control study in Han Chinese

Introduction

Developmental dysplasia of the hip (DDH) is a common skeletal disease, which is characterized by abnormal seating of the femoral head in the acetabulum. Genetic factors play a considerable role in the etiology of DDH. Asporin (ASPN) is an ECM protein which can bind to TGF-β1 and sequentially inhibit TGF-β/Smad signaling. A functional aspartic acid (D) repeat polymorphism of ASPN was first described as an osteoarthritis-associated polymorphism. As TGF-β is well known as an important regulator in the development of skeletal components, ASPN may also be involved in the etiology of DDH. Our objective is to evaluate whether the D repeat polymorphism of ASPN is associated with DDH in Han Chinese.

Methods

The D repeat polymorphism was genotyped in 370 DDH patients and 445 control subjects, and the allelic association of the D repeat was examined.

Results

From D11 to D18, eight alleles were identified. D13 allele is the most common allele both in control and DDH groups, the frequencies are 67.3% and 58.1% respectively. In the DDH group, a significantly higher frequency of the D14 allele and significantly lower frequency of D13 was observed. The association of D14 and D13 was found in both females and males after stratification by gender. There was no significant difference in any other alleles we examined.

Conclusions

Our results show an obvious association between the D repeat polymorphism of ASPN and DDH. It indicates that ASPN is an important regulator in the etiology of DDH.     

A single-nucleotide polymorphism of the TNFAIP3 gene is associated with systemic lupus erythematosus in Chinese Han population

Systemic lupus erythematosus (SLE) is a complex systemic disease influenced by genetic and environmental factors. The exact pathogenesis of SLE is still unknown. Recently, several genome-wide association studies (GWA) in European population have found many novel susceptibility genes for SLE including TNFAIP3. In order to examine whether TNFAIP3 is associated with SLE in Chinese Han population, we genotyped one of its non-synonymous mutation SNP rs2230926, showing significant association evidence with SLE in European population, with 1,420 cases and 4,461 controls of Chinese Han by using Sequenom MassArray system. Highly significant association between SNP rs2230926 and SLE of Chinese Han was detected [OR = 1.65, 95% confidence interval (CI): 1.392–1.986, P = 2.03 × 10⁻⁸]. Interestingly, rs2230926 of TNFAIP3 was also associated with arthritis, ANA and some other subphenotypes of the disease. Our findings suggest that SNP rs2230926 in the TNFAIP3 might be a common genetic factor for SLE within different populations in terms of Chinese Han and European population.