Glucocorticoid Receptor Gene Polymorphisms Research Articles

Association of glucocorticoid receptor gene polymorphism and occupational stress with hypertension in desert petroleum workers in Xinjiang, China

BackgroundThe aim of this study was to investigate the occupational stress and hypertension in desert petroleum workers in Xinjiang, and to analyze the association of occupational stress and glucocorticoid receptor (GR) gene polymorphism with the presence of hypertension.MethodsUsing cluster sampling, 1280 desert petroleum workers of 3 petroleum fields in Xinjiang Karamay were randomly selected as the target group for this study. According to the inclusion criteria, a total of 1080 workers were included as the baseline for this study. We followed these workers for 2 years to investigate their occupational stress and hypertension. The polymorphism of GR gene was detected by polymerase chain reaction-restriction fragment length polymorphism. We applied appropriate statistical methods to analyze the association of occupational stress and glucocorticoid receptor (GR) gene polymorphism with the presence of hypertension.ResultsAfter 2 years of follow-up, there were 995 desert petroleum workers in the queue. The study showed that the incidence of hypertension in desert petroleum workers were 19.4%. Compared with the baseline data, the level of occupational stress increased, and with the increase of occupational stress, the incidence of hypertension was gradually increasing. A positive relationship was observed in the GR BCL1 gene polymorphisms and hypertension. Relative to the CC genotype, carries of the GG genotype had a significantly higher risk of hypertension (OR = 2.830). With the combination of genotype CG and GG, carries of CG and GG increased the risk of hypertension (adjusted OR = 2.238, 95%CI:1.104–4.940). There was no significant association between GR G678S gene polymorphisms and hypertension.ConclusionGR gene polymorphism and occupational stress of desert petroleum workers were important risk factors for hypertension.

A Study of Glucocorticoid Receptor Gene Polymorphism (BclI) in Egyptian patients with Rheumatoid Arthritis

A Study of Glucocorticoid Receptor Gene Polymorphism (BclI) in Egyptian patients with Rheumatoid Arthritis

Association between polymorphisms of glucocorticoid receptor genes and asthma: A meta-analysis

Recent studies have evaluated the associations between polymorphisms of glucocorticoid receptor genes and asthma. However, the conclusions of these studies are conflicting. The objective of this meta-analysis was to clarify the association between all known polymorphisms of glucocorticoid receptor genetic loci and susceptibility to asthma, based on existing reports. We conducted a meta-analysis of the association between glucocorticoid receptor polymorphisms (NR3C1) and asthma risk. A systematical literature search was performed in PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), and Cochrane Library until January 15, 2018. The odds ratio (OR), 95% confidence interval (CI), and P value were calculated using Mantel-Haenszel statistics under the allele, homozygote, heterozygote, dominant, or recessive models. P values of less than 0.05 were considered to represent statistically significant associations between glucocorticoid receptor gene polymorphisms and asthma. All statistical analyses were done using the "meta" package (version 4.9-0) of R version 3.4.3 and RStudio version 1.0.44. A total of fourteen studies, reported via ten articles from online databases were included in our meta-analysis. For BclI (from eight studies), a significant association was detected in the allele model, homozygote model, and recessive model (C versus G: OR (95% CI) = 0.63 (0.40-0.97), CC versus GG: OR (95% CI) = 0.41(0.17-0.97), CC versus GC + GG: OR (95% CI) = 0.54(0.34-0.88)), but not in the heterozygote model or the dominant model. For ER22/23EK (from four studies), TthIII1 (from two studies), no significant association was found for any genetic model. After subgroup analyses by age, significant associations were observed for the allele model, homozygote model, dominant model and recessive model for BclI in adults. The ER22/23EK and TthIII1 polymorphisms were not found to be associated with susceptibility to ASTHMA; however, the BclI polymorphisms were significantly associated with ASTHMA in adults.

Blunt response to a stress test and higher prevalence of risk polymorphism of glucocorticoid receptor gene (NC3C1) in obese patients

Blunt response to a stress test and higher prevalence of risk polymorphism of glucocorticoid receptor gene (NC3C1) in obese patients

Association of glucocorticoid receptor gene polymorphisms with systemic lupus erythematosus in a Chinese population.

To identify the association of glucocorticoid receptor (GR) gene polymorphism with systemic lupus erythematosus (SLE). A case-control study was carried out, in which 400 Chinese patients with SLE and 400 normal people were enrolled. DNA was extracted using a genomic DNA extraction kit, and tagged single nucleotide polymorphisms (SNPs) were identified by Haploview (4.0) Project from the Chinese HapMap Project. Eighteen tagged SNPs of the GR gene were genotyped by the Multiplex SNaPshot technique. Two GR gene SNPs were associated with the pathogenesis of SLE: rs6865292 (dominant model: crude odds ratio [OR] = 1.526, 95% CI: 1.151-2.025, P = 0.003; adjusted OR = 1.525, 95% CI: 1.149-2.023, P = 0.004; PBH = 0.036) and rs9324921 (dominant model: crude OR = 1.556, 95% CI: 1.173-2.062, P = 0.002; adjusted OR = 1.553, 95% CI: 1.171-2.060, P = 0.002; PBH = 0.036). The haplotype analysis of GR gene SNPs manifested that the haplotype of 'CCGGG' (OR = 2.701, 95% CI: 1.348-5.410, P = 0.004; PBH = 0.036) was a risk factor for the development of SLE. A lower frequency of A-allele of SNP rs4607376 (P = 0.021; OR = 0.794, 95% CI: 0.652-0.966, PBH = 0.126), higher frequency of C-allele of SNP rs6865292 (P = 0.019, OR = 1.317, PBH = 0.126) and A-allele of SNP rs9324921 (P = 0.019, OR = 1.317, PBH = 0.126) may be risk factors for developing SLE. The rs7719514 (recessive model: crude P = 0.044; adjusted P = 0.044, PBH = 0.264), rs7701443 (recessive model: crude P = 0.044, adjusted P = 0.045; PBH = 0.264), rs4607376 (recessive model: crude P = 0.027; adjusted P = 0.026; PBH = 0.264) and haplotype 'CAGCG' (P = 0.044; PBH = 0.198) showed marginal association with the pathogenesis of SLE. In the case group, there were no significant differences between non-lupus nephritis and lupus nephritis. Further, we found that the SNP rs12054797 (F = 3.228, P = 0.041, PBH = 0.342), rs2963156 (F = 3.163, P = 0.043, PBH = 0.342) might be marginally associated with disease activity. The study indicates that GR genetic polymorphisms may play a major role in the pathogenesis and development of SLE.

A polymorphism in the glucocorticoid receptor gene is associated with refractory hypotension in premature infants

Glucocorticoids play an important role in endocrine control. The association of glucocorticoid receptor (GR) gene polymorphisms with altered sensitivity to glucocorticoid therapy has been reported in adults. However, there are few such reports in infants. The present study analyzed the prevalence of four GR polymorphisms in preterm infants born before 30 weeks of gestation and determined the associations between these polymorphisms and clinical outcomes in the infants. Totally, 41 preterm infants born at two hospitals in Fukushima were retrospectively screened for the presence of four GR gene polymorphisms, using a TaqMan single-nucleotide polymorphism genotyping assay. The effect of GR gene polymorphisms on clinical outcomes during hospitalization was evaluated. The following primary clinical outcomes were assessed: refractory hypotension in the acute phase and/or severe bronchopulmonary dysplasia, maximum dopamine and dobutamine doses administered, and total hydrocortisone dose administered in the first 48h of life. Multivariate analysis with logistic regression was used to assess the association between clinical factors and refractory hypotension. Of the four GR polymorphisms, only the BclI polymorphism was detected. The genotype distribution was as follows: C/C, 33; C/G, 8; and G/G, 0 infants. Significant differences were observed between the C/C and C/G genotypes with respect to the following variables: refractory hypotension (6% vs. 50%), dopamine dose [3.0 (2.0-4.0) vs. 4.8 (4.0-7.5) μg/kg/min], dobutamine dose [2.4 (0.0-3.6) vs. 4.0 (0-10.0) μg/kg/min], and total hydrocortisone dose administered in the first 48h of life [2.0 (0-10.0) vs. 6.0 (0-12.0) mg/kg]. Multivariate analysis showed that the BclI genotype (C/C) was significantly less associated with refractory hypotension in the acute phase (odds ratio, 0.008; 95% confidence interval, 0.000-0.371; p=0.013). The incidence of refractory hypotension in infants with the C/C genotype was initially expected to be higher than that in infants with the C/G genotype. However, the results of this study were rather different from what we originally expected. The suppressive effect of antenatal steroid use on the HPA axis of the preterm infants with the BclI variant may be associated with refractory hypotension in the acute phase.

BclI polymorphism of the glucocorticoid receptor and adrenal crisis in primary adrenal insufficiency.

ContextPatients with primary adrenal insufficiency (PAI) or congenital adrenal hyperplasia (CAH) are at a high risk of adrenal crisis (AC). Glucocorticoid sensitivity is at least partially genetically determined by polymorphisms of the glucocorticoid receptor (GR).ObjectivesTo determine if a number of intercurrent illnesses and AC are associated with the GR gene polymorphism BclI in patients with PAI and CAH.Design and patientsThis prospective, longitudinal study over 37.7 ± 10.1 months included 47 PAI and 25 CAH patients. During the study period, intercurrent illness episodes and AC were documented.ResultsThe study period covered 223 patient years in which 21 AC occurred (9.4 AC/100 pat years). There were no significant differences between BclI polymorphisms (CC (n = 29), CG (n = 34) and GG (n = 9)) regarding BMI, hydrocortisone equivalent daily dose and blood pressure. We did not find a difference in the number of intercurrent illnesses/patient year among BclI polymorphisms (CC (1.5 ± 1.4/pat year), CG (1.2 ± 1.2/pat year) and GG (1.6 ± 2.2/pat year)). The occurrence of AC was not significantly different among the homozygous (GG) genotype (32.5 AC/100 pat years), the CC genotype (6.7 AC/100 pat years) and the CG genotype (4.9 AC/100 pat years). Concomitant hypothyroidism was the highest in the GG genotype group (5/9), compared to others (CC (11/29) and CG (11/34)).ConclusionsAlthough sample sizes were relatively small and results should be interpreted with caution, this study suggests that the GR gene polymorphism BclI may not be associated with the frequencies of intercurrent illnesses and AC.

Genetic Associations and Interactions Between the NR3C1 (GR) and NR3C2 (MR) Genes and Aggressive Behavior in a Central South Chinese Han Population.

The glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) play important roles in the hypothalamic-pituitary-adrenal axis and stress regulation. The current study aimed to address the genetic association and gene-gene interactions between GR and MR gene polymorphisms and aggressive behavior. A haplotype-based, case-control study was designed to examine the association between human MR and GR genes and aggressive behaviors, including robbery and intentional interpersonal injury, in a central south Chinese Han population. Eight well-studied polymorphisms of the MR gene (rs2070951, rs2871, rs5522, and rs5525) and the GR gene (rs10482605, rs6190, rs1800445, and rs6196) were genotyped using SNaPshot. The MR and GR gene polymorphisms were not associated with aggressive behaviors, including in robbery and intentional interpersonal injury subgroups (p > 0.05). The frequency of haplotype TAAT of GR was significantly higher in the control group than that in the case group (p = 0.004, padj = 0.02). In addition, a two-way interaction between GR rs1800445 and MR rs2070951 and aggressive behavior was also found (p = 0.01). The haplotype TAAT of GR might be a protective factor against aggressive behavior, while gene-gene interactions between GR rs1800445 and MR rs2070951 might be a risk factor for aggressive behavior in the Central South Chinese Han population.

Mechanisms of Brain Glucocorticoid Resistance in Stress-Induced Psychopathologies.

Exposure to stress activates the hypothalamic-pituitary-adrenal axis and leads to increased levels of glucocorticoid (GC) hormones. Prolonged elevation of GC levels causes neuronal dysfunction, decreases the density of synapses, and impairs neuronal plasticity. Decreased sensitivity to glucocorticoids (glucocorticoid resistance) that develops as a result of chronic stress is one of the characteristic features of stress-induced psychopathologies. In this article, we reviewed the published data on proposed molecular mechanisms that contribute to the development of glucocorticoid resistance in brain, including changes in the expression of the glucocorticoid receptor (GR) gene, biosynthesis of GR isoforms, and GR posttranslational modifications. We also present data on alterations in the expression of the FKBP5 gene encoding the main component of cell ultra-short negative feedback loop of GC signaling regulation. Recent discoveries on stress- and GR-induced changes in epigenetic modification patterns as well as normalizing action of antidepressants are discussed. GR and FKBP5 gene polymorphisms associated with stress-induced psychopathologies are described, and their role in glucocorticoid resistance is discussed.

Glucocorticoid receptor gene polymorphisms in hereditary angioedema with C1-inhibitor deficiency

BackgroundHereditary angioedema caused by C1-inhibitor deficiency (C1-INH-HAE) is a rare, autosomal dominant disorder. C1-INH-HAE is characterized by edema–formation, which may occur in response to stress. The individual’s response to stress stimuli is partly genetically determined. Activation of the hypothalamic–pituitary–adrenal axis results in the release of cortisol. In turn, the secreted gluco- and mineralocorticoids affect the metabolism, as well as the cardiovascular and immune systems. We hypothesized that changes in serum cortisol level and polymorphisms of the glucocorticoid receptor (GR) modify the individual sensitivity to stressor stimuli of C1-INH-HAE patients.ResultsWe compared the response to stress with Rahe’s Brief Stress and Coping Inventory of 43 C1-INH-HAE patients, 18 angioedema patients and 13 healthy controls. 139 C1-INH-HAE patients and 160 healthy controls were genotyped for glucocorticoid receptor polymorphisms BclI, N363S and A3669G. Serum cortisol levels were determined during attacks and during symptom-free periods in 36 C1-INH-HAE patients. The relationships between clinical, laboratory data and GR SNPs (Single Nucleotide Polymorphisms) were assessed using ANOVA. C1-INH-HAE patients have decreased coping capabilities compared to healthy controls. Cortisol levels were significantly higher during attacks than in symptom-free periods (p = 0.004). The magnitude of the elevation of cortisol levels did not show a significant correlation with any clinical or laboratory data. Among the C1-INH-HAE patients, the carriers of the A3669G allele had significantly lower cortisol levels, and increased body mass index compared with non-carriers.ConclusionsThe higher cortisol level observed during attacks may reflect the effect of a stressful situation (such as of the attack itself), on the patients’ neuroendocrine system. In A3669G carriers, the lower cortisol levels might reflect altered feedback to the hypothalamic–pituitary–adrenal axis, due to decreased sensitivity to glucocorticoids.

Investigation of glucocorticoid receptor and calpain-10 gene polymorphisms in Turkish patients with type 2 diabetes mellitus

Background/aim: We proposed to investigate the role of calpain-10 (CAPN10) gene single nucleotide polymorphism (SNP)-19 and SNP-44 and glucocorticoid receptor (NR3C1) gene N363S polymorphisms in Turkish patients with type 2 diabetes mellitus (T2DM).Materials and methods: Peripheral blood samples were obtained from 125 patients with T2DM and 112 healthy volunteers. Genotyping was carried out by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: There were no statistically significant differences found between the allele and genotype frequencies of CAPN10 SNP-19, CAPN10 SNP-44, and NR3C1 N363S polymorphisms and T2DM development (P > 0.05). The CAPN10 SNP-19 del-allele, CAPN10 SNP-44 C-allele, and NR3C1 N363S G-allele were determined to be risk factors for T2DM development. In T2DM patients an association was identified between the CAPN10 SNP-19 del-allele, homozygous del/del genotype, SNP-44 C-allele, heterozygous TC genotype, NR3C1 N363S G-allele, heterozygous AG genotype, and increased BMI. Conclusion: The present study demonstrates that the SNP-44 polymorphism is associated with T2DM susceptibility and contributes to the risk of T2DM.

Glucocorticoid Receptor (NR3C1) Gene Polymorphism Moderate Intervention Effects on the Developmental Trajectory of African-American Adolescent Alcohol Abuse.

Accumulative evidence from recent genotype × intervention studies suggests that individuals carrying susceptible genotypes benefit more from intervention and provides one avenue to identify subgroups that respond differentially to intervention. This study examined the moderation by glucocorticoid receptor (NR3C1) gene variants of intervention effects on the developmental trajectories of alcohol abuse through adolescence. Participants were randomized into Fast Track intervention and control groups self-reported past-year alcohol abuse annually from grade 7 through 2years post-high school and provided genotype data at age 21 (69% males; European Americans [EAs] = 270, African-Americans [AAs] = 282). Latent growth curve models were fit to examine developmental trajectories of alcohol abuse. The interactions of 10 single nucleotide polymorphisms (SNPs) in NR3C1 with intervention were examined separately. Both EAs and AAs showed significant increases in past-year alcohol abuse with substantial inter-individual differences in rates of linear growth. AAs showed lower general levels and slower rates of linear growth than EAs. Adjusting for multiple tests, one NR3C1 SNP (rs12655166) significantly moderated intervention effects on the developmental trajectories of alcohol abuse among AAs. Intervention effects on the rates of linear growth were stronger among AAs carrying minor alleles than those not carrying minor alleles. The findings highlight the importance of taking a developmental perspective on adolescent alcohol use and have implications for future intervention design and evaluation by identifying subgroups that could disproportionally benefit from intervention.

Glucocorticoid Receptor Gene Variants and Neonatal Outcome in Very-Low-Birth-Weight Preterm Infants

Background: Induction of lung maturation by prenatal steroid treatment has become the standard of care for pregnant women at risk for preterm birth. In addition to the beneficial effects on lung maturation, prenatal steroids have been shown to reduce the incidence of neonatal death, necrotizing enterocolitis, sepsis, and intraventricular hemorrhage. However, little is known about the role of interindividual differences in corticoid sensitivity arising from polymorphisms in the glucocorticoid receptor (GR) gene. Objectives: To assess the impact of GR polymorphisms N363S (rs56149945), R23K (rs6190), and BclI (rs41423247) on neonatal outcome. Methods: The GR polymorphisms N363S, R23K, and BclI were examined in 10,490 very-low-birth-weight (VLBW) preterm infants from 49 German tertiary level neonatal units (German Neonatal Network, GNN) with respect to neonatal outcome. Results: Infants carrying the BclI genotype were at higher risk to develop bronchopulmonary dysplasia (BPD) (OR 1.12 per BclI allele, 95% CI: 1.02-1.23, p = 0.013) in a logistic regression model adjusted for gestational age, mechanical ventilation, and small for gestational age status. A similar relative risk was seen in the children (89.4%) who received antenatal betamethasone treatment (OR 1.16, 95% CI: 1.05-1.27, p = 0.003), whereas no such effect was detectable in infants without antenatal steroids. N363S and R23K did not show any stable association with neonatal outcome parameters. Conclusion: Except for a slightly higher risk of BPD in carriers of the GRBclI variant, the GR gene polymorphisms BclI, N363S, and R23K did not affect neonatal outcome parameters in this large multicenter cohort of VLBW preterm infants.

Associations between the neuron-specific glucocorticoid receptor (NR3C1) Bcl-1 polymorphisms and suicide in cancer patients within the first year of diagnosis.

BackgroundCancer diagnosis is associated with an increased suicide risk, particularly within the first 1 year after diagnosis of cancer. Abnormal function of the hypothalamic–pituitary–adrenal axis has been implicated in the pathophysiology of depression and suicide. We examined genetic associations of the functional Bcl-1 polymorphism of (rs41423247) neuron-specific glucocorticoid receptor (NR3C1) gene, with death by suicide in cancer patients. Suicides occurring within a year of cancer diagnosis (‘early suicide’) were considered separately from those suicides during the second or subsequent year (‘late suicide’) after cancer diagnosis.MethodsThe subjects consisted of 343 cancer patients admitted to a general hospital in Seoul, South Korea from 1996 to 2009, of which 182 had died by suicide and 161 were alive on December 31, 2009. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue sample of patients with cancer. We conducted a case-control association analysis of Bcl-1 polymorphism of NR3C1 gene.ResultsSubjects carrying the GG genotype of Bcl-1 polymorphism were at increased risk of early suicide when compared to those carrying the CC genotype (OR 3.80, 95 % CI 1.02–14.16, p = .047). Similarly, those individuals carrying the GG genotype (recessive mode) had an increased risk of early suicide relative to the CC or CG genotype (OR 3.71, 95 % CI 1.03–13.43, p = .045). However, there were no differences in the genotype distributions of the NR3C1 Bcl-1 polymorphism between late suicide cases and controls.ConclusionsOur findings suggest that the NR3C1 Bcl-1 polymorphisms may be involved in the susceptibility to suicide within the first year after cancer diagnosis among cancer patients in Korean population.

Analyses of the role of the glucocorticoid receptor gene polymorphism (rs41423247) as a potential moderator in the association between childhood overweight, psychopathology, and clinical outcomes in Eating Disorders patients: A 6 years follow up study

Childhood overweight and the SNP rs41423247 of the glucocorticoid receptor gene (GR) were reported to represent predisposing factors for Eating Disorders (EDs). The distribution of the polymorphism was evaluated in 202 EDs patients, and in 116 healthy subjects. The Structured Clinical Interview for the DSM-IV and self-reported questionnaires were administered at the admission to the clinic and at 3 time points (end of a cognitive behavioral therapy, 3 and 6 years follow up). G-allele was associated with childhood overweight, depressive disorder comorbidity, and diagnostic instability. G-allele carriers reporting childhood overweight showed greater frequency of subjective binge eating and emotional eating.

Bcl1 polymorphism of glucocorticoid receptor gene in patients with bronchial asthma with obesity

The objective of this investigation was to analyze possible association between BclI polymorphism of glucocorticoid receptor gene and obesity in patients with bronchial asthma (BA). The study involved 188 patients with bronchial asthma and 95 apparently healthy adult individuals. Generally accepted assessments and examinations for BA diagnosis, and anthropometric, molecular-genetic and statistic methods of investigation were used in the research. It was found out that the patients with BA demonstrated higher body mass index (BMI) and higher ratio of fat centralization much more often, than the control group. Genotypes distribution for BclI polymorphism in patients with BA showed a statistically significant difference between patients with different BMI unlike the control group. Comparison of genotype frequency for BclI polymorphism in glucocorticoid receptor gene in individuals with different ratio of fat centralization in the control group and in the patients with BA separately showed statistically significant differences in the distribution of gene allelic variations only among the patients with BA. It was demonstrated that G/G genotype in the patients with visceral obesity was associated with BA.

Sequencing analysis of the human glucocorticoid receptor (NR3C1) gene in multiple sclerosis patients

Various specific human glucocorticoid receptor (NR3C1) gene polymorphisms have been described in multiple sclerosis (MS) patients and correlated with disease progression, susceptibility and aggressiveness. Herein, we investigated the presence of gene alterations in the entire coding region of the NR3C1 in MS patients of variable clinical status (CIS, RRMS and SPMS) and the association(s) of these alterations with severity of disease (EDSS), response to glucocorticoid (GC) treatment and clinical improvement. Sixty Caucasian Greek MS patients were included. Sequencing the coding sequences and intron-exon boundaries of the NR3C1 did not reveal the presence of mutation(s) in any of the MS patients. Three previously described polymorphisms were detected: p.N363S (rs6195), p.N766N (rs6196) and c.1469-16G>T (rs6188). None of the identified alleles/genotypes were found to be associated with the severity of disease, response to glucocorticoids and disease subtypes. Known polymorphism, such as ER22/23EK that has been previously detected in MS patients, was not detected. There is a considerable ethnicity-related variation in the frequency of the NR3C1 polymorphisms. Although a genetic basis of the glucocorticoid sensitivity exists in healthy population, in the presence of chronic inflammation and abundance of cytokines - such in MS patients - other factors appear to play a more important role in GC sensitivity.

Impact of glucocorticoid receptor gene (NR3C1) polymorphisms in Turkish patients with metabolic syndrome

The metabolic syndrome (MetS) is characterized by a cluster of metabolic factors, including insulin resistance and type-2 diabetes, abdominal obesity, dyslipidemia, hypertension and microalbuminuria. Impaired glucocorticoid receptor (GR) activity also plays an important role in the etiology of MetS. The objective of our study is to evaluate the effects of GR gene polymorphisms (BclI, N363S, TthIII1 and ER22/23EK) in Turkish patients with MetS. Seventy subjects with MetS and 185 healthy controls were enrolled in the study. PCR-RFLP analysis was used for genotyping. Results for each polymorphism have been verified by allele-specific oligonucleotide analysis. BclI GG genotype was significantly associated with an increased risk of MetS (p = 0.02). Also, only in women, the G allele carriers were significantly associated with higher C-peptide. T allele carriers of TthIII1 polymorphism were significantly associated with higher C-peptide, triglyceride, insulin and C-reactive protein (CRP, p value 0.048, 0.022, 0.005 and 0.022, respectively), and lower fasting blood glucose (FBG, p = 0.02). The combined carriers of BclI polymorphism G allele and TthIII1 polymorphism T allele were significantly associated with higher diastolic blood pressure in all patients, and lower FBG and postprandial blood glucose in only men. All the ER22/23EK polymorphisms coexisted with polymorphic variant of TthIII1 (p = 0.0058). The presence of homozygote polymorphic variant of BclI might be good predictive markers for the disease susceptibility. The BclI and the TthIII1 polymorphism are associated with sex-specific clinical parameters. Our findings also suggest that the combination of BclI and TthIII1 polymorphisms may play a protective role in blood glucose.

Impact of the glucocorticoid receptor BclI polymorphism on reward expectancy and prediction error related ventral striatal reactivity in depressed and healthy individuals.

There is evidence that reward-related neural reactivity is altered in depressive disorders. Glucocorticoids influence dopaminergic transmission, which is widely implicated in reward processing. However, no studies have examined the effect of glucocorticoid receptor gene polymorphisms on reward-related neural reactivity in depressed or healthy individuals. Fifty-nine depressed individuals with major depressive disorder (n=33) or bipolar disorder (n=26), and 32 healthy individuals were genotyped for the glucocorticoid receptor BclI G/C polymorphism, and underwent functional magnetic resonance imaging during a monetary reward task. We examined the effect of the glucocorticoid receptor BclI G/C polymorphism on reward expectancy (RE; expected outcome value) and prediction error (PE; discrepancy between expected and actual outcome) related ventral striatal reactivity. There was a significant interaction between reward condition and BclI genotype (p=0.007). C-allele carriers showed higher PE than RE-related right ventral striatal reactivity (p<0.001), whereas no such difference was observed in G/G homozygotes. Accordingly, C-allele carriers showed a greater difference between PE and RE-related right ventral striatal reactivity than G/G homozygotes (p<0.005), and also showed lower RE-related right ventral striatal reactivity than G/G homozygotes (p=0.011). These findings suggest a slowed transfer from PE to RE-related ventral striatal responses during reinforcement learning in C-allele carriers, regardless of diagnosis, possibly due to altered dopamine release associated with increased sensitivity to glucocorticoids.

Glucocorticoid receptor genetic polymorphisms is associated with improvement of health-related quality of life in Chinese population with systemic lupus erythematosus.

In our previous study, we found that glucocorticoid receptor (GR) gene genetic polymorphisms may play a major role in the efficacy of glucocorticoids (GCs) in Chinese systemic lupus erythematosus (SLE) patients. The aim of this study is to explore the association of GR gene genetic polymorphisms and improvement of health-related quality of life (HRQOL) in Chinese SLE patients treated with GCs. A total of 195 Chinese SLE patients were treated with GCs for 12 weeks. The HRQOL of patients was measured with the Medical Outcomes Study Short Form-36 (SF-36) at baseline and 12 weeks. Polymorphisms of GR gene were genotyped by using multiplex SNaPshot method. One hundred eighty-four patients (94.36 %) completed the 12-week follow-up. Twenty-three single-nucleotide polymorphisms of GR gene were genotyped. There was a significant association between rs10482672 polymorphism and improvement in physical function (P = 0.043), general health (P = 0.024), and social function (P = 0.013). The rs12656106 polymorphism was associated with improvement in the total score of SF-36 (P = 0.014), physical function (P = 0.013), general health (P = 0.010), vitality (P = 0.015), social function (P = 0.004), physical component summary (P = 0.016), and mental component summary (P = 0.014). The rs4912905 polymorphism was associated with improvement in bodily pain (P = 0.040) and general health (P = 0.038). The rs4912911 polymorphism was associated with improvement in general health (P = 0.026) and vitality (P = 0.027). The rs4986593 polymorphism was associated with improvement in bodily pain (P = 0.034). The rs7719514 polymorphism was associated with improvement in vitality (P = 0.002) and mental component summary (P = 0.041). We also found a significant association between rs9324924 polymorphism and improvement in physical function (P = 0.040), bodily pain (P = 0.007), and general health (P = 0.019). These results indicate that there may be an association of GR gene rs10482672, rs12656106, rs4912905, rs4912911, rs4986593, rs7719514, and rs9324924 polymorphisms with improvement of HRQOL in Chinese SLE patients treated with GCs.