Association of job stress,CLOCK gene polymorphism and their interaction with poor sleep quality

Job stress and the Circadian Locomotor Output Cycles Kaput (CLOCK) gene could affect circadian rhythm and sleep quality. The main aim of our present study was to investigate the association of job stress, CLOCK gene polymorphism and their interaction with sleep quality in a non‐clinical Chinese Han population, which has not been reported to date. Using a cross‐sectional design, 450 subjects were recruited in Beijing. Sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI) and job stress was measured with the Work Stress Scale. CLOCK gene rs11932595 polymorphism was genotyped in 297 blood samples. Correlation analysis showed a close but different association of high job stress with the PSQI and its components. Analysis of variance showed significant main effects of the CLOCK gene rs11932595 polymorphism. G‐allele carriers had a higher score in the PSQI, sleep duration, sleep latency and sleep disturbances. Further interaction analyses showed an ordinal interaction on sleep duration, and a disordinal interaction on daytime dysfunction. Specifically, G‐allele carriers had poorer sleep duration than AA homozygotes when in high job stress, while the two subgroups displayed similar sleep duration when in low job stress, conforming to the diathesis–stress model. In comparison to G‐allele carriers, AA homozygotes experienced less daytime dysfunction when in low job stress whereas more daytime dysfunction when in high job stress, fitting with the differential susceptibility model. As genetic links have been revealed, our investigation might be conducive for elucidating aetiological factors for sleep quality and targets for implementing interventions to attain good sleep quality.     

Scavenger receptor class B type I genetic variants associated with disease severity in chronic hepatitis C virus infection

Analysis of host genetic polymorphisms is an increasingly important tool for understanding and predicting pathogenesis and treatment response of viral diseases. The gene locus of scavenger receptor class B type I (SR-BI), encoding a cell entry factor and receptor for hepatitis C virus (HCV), contains several genetic polymorphisms. We applied a probe extension assay to determine the frequency of six single nucleotide polymorphisms (SNPs) within the SR-BI gene locus in 374 individuals with history of HCV infection. In addition, SR-BI messenger RNA (mRNA) levels were analyzed in liver biopsy specimens of chronically infected HCV subjects. The rs5888 variant allele T was present at a higher frequency in subjects with advanced fibrosis (χ², p = 0.016) and after adjusting for age, duration of infection and alcohol intake as confounding factors. Haplotype analysis of SNP frequencies showed that a haplotype consisting of rs61932577 variant allele C and rs5888 variant allele T was associated with an increased risk of advanced liver fibrosis (defined by an Ishak score 4−6) (adjusted odds ratio 2.81; 95% confidence interval 1.06−7.46. p = 0.038). Carriers of the rs5888 variant allele T displayed reduced SR-BI mRNA expression in liver biopsy specimens. In conclusion the rs5888 polymorphism variant is associated with decreased SR-BI expression and an increased risk of development of advanced fibrosis in chronic HCV infection. These findings provide further evidence for a role of SR-BI in HCV pathogenesis and provides a genetic marker for prediction of those infected individuals at greater risk of developing severe disease.     

The natural killer cell-associated rs9916629-C allele is a novel genetic risk factor for fatal COVID-19

The severity of COVID-19 is associated with individual genetic host factors. Among these, genetic polymorphisms affecting natural killer (NK) cell responses, as variations in the HLA-E- (HLA-E*0101/0103), FcγRIIIa- (FcγRIIIa-158-F/V), and NKG2C- (KLRC2^wt/del) receptor, were associated with severe COVID-19. Recently, the rs9916629-C/T genetic polymorphism was identified that indirectly shape the human NK cell repertoire towards highly pro-inflammatory CD56^bright NK cells. We investigated whether the rs9916629-C/T variants alone and in comparison to the other risk factors are associated with a fatal course of COVID-19. We included 1042 hospitalized surviving and 159 nonsurviving COVID-19 patients as well as 1000 healthy controls. rs9916629-C/T variants were genotyped by TaqMan assays and were compared between the groups. The patients' age, comorbidities, HLA-E*0101/0103, FcγRIIIa-158-F/V, and KLRC2^wt/del variants were also determined. The presence of the rs9916629-C allele was a risk factor for severe and fatal COVID-19 (p < 0.0001), independent of the patients' age or comorbidities. Fatal COVID-19 was more frequent in younger patients (<69.85 years) carrying the FcγRIIIa-158-V/V (p < 0.006) and in older patients expressing the KLRC2^del variant (p < 0.003). Thus, patients with the rs9916629-C allele have a significantly increased risk for fatal COVID-19 and identification of the genetic variants may be used as prognostic marker for hospitalized COVID-19 patients.     

rs798766 C＞T多态性与膀胱癌易感性的Meta分析

目的 对rs798766 C>T多态性与膀胱癌易感性的关联进行Meta分析.方法 在Pubmed与百度学术数据库中检索相关病例对照研究,根据纳入与排除标准进行筛选.提取研究基本情况,提取或计算T等位基因比值比ORCT+TT vs.CC及其95 %可信区间,进行Meta分析.结果 共纳入9项病例对照研究,涉及10 647名膀胱癌患者与53 588名健康对照.Meta分析有显著异质性(I2=75 %,P<0.1),合并结果为1.34[1.19,1.51].亚组分析结果显示,亚洲人与白人的合并结果无显著差异(χ2=0.65,P=0.42).漏斗图对称,无发表偏倚.结论 rs798766 C>T多态性增加膀胱癌易感性.     

The Fc receptor-like 3 gene polymorphisms and susceptibility to autoimmune diseases: An updated meta-analysis

Abstract

Previous studies have identified several single nucleotide polymorphisms (SNPs) of Fc receptor-like 3 (FCRL3), an excellent susceptibility gene, as predisposing factors for human autoimmune diseases (ADs). However, the results remain inconclusive. To assess the effect of four selected SNPs (rs7528684, rs11264799, rs945635 and rs3761959), we conducted a meta-analysis with 34 case-control studies. Summary odd ratios (ORs) and 95% confidence intervals (95% CIs) for the polymorphisms in FCRL3 and ADs risk were evaluated. Furthermore, this meta-analysis was performed by using allele comparisons, as well as stratified analyses by ethnicity and disease phenotypes under different genetic models. Our data showed that the TC, TT?+?TC genotypes of rs7528684 contributed to a lower risk of ADs, compared with the CC carriers (OR?=?0.91, 95% CI?=?0.85–0.97; OR?=?0.91, 95% CI?=?0.85–0.98). In comparison with rs7528684 TC genotype, the TT?+?CC carriers were significantly associated with higher ADs risk (OR?=?1.03, 95% CI?=?1.00–1.07). In terms of stratified analyses by ethnicity and disease phenotypes, there were significant associations of rs7528684 polymorphism both with ADs in Asians and Europeans, and with rheumatoid arthritis, Graves’ disease, type-1 diabetes, and other ADs under different genetic models. Moreover, significant associations were also found to be correlated with ADs risk for the SNP rs11264799 in mixed subgroup, for rs945635 in Europeans, North Americans and mixed group, and for rs3761959 in North Americans. These findings indicate that the polymorphisms in FCRL3 may play a role in the pathogenesis of ADs.     

Is the CARD8 rs2043211 polymorphism associated with susceptibility to Crohn’s disease? A meta-analysis

Abstract

Many studies have reported the association between the CARD8 gene polymorphism rs2043211 and the susceptibility to Crohn’s disease (CD), but the results have remained quite contradictory. Therefore, the aim of the meta-analysis was to explore whether the CARD8 rs2043211 polymorphism has an effect on CD risk. We performed a systematic literature search for related articles published up to July 2014 in multiple databases. Six eligible articles containing eight studies were selected. Odds ratios (ORs) as well as their corresponding 95% confidence intervals (CIs) were used to estimate the association between the CARD8 polymorphism and CD risk in different genotypic models. Heterogeneity analysis was also performed and publication bias was taken into account. Subgroup analyses were conducted according to different ethnicities, as well as different types of CD. In the pooled analyses, no statistical significant association was found between the CARD8 polymorphism and CD risk in the overall population or Caucasian subgroup in the additive model (overall population: OR?=?0.93, 95% CI?=?0.87–1.01; Caucasian: OR?=?0.93, 95% CI?=?0.83–1.05). However, subgroup analysis based on different CD types showed a significant association between the CARD8 polymorphism and CD risk in the additive model (ileal CD: OR?=?0.83, 95% CI?=?0.70–0.98; stenotic or fistulizing CD: OR?=?0.81, 95% CI?=?0.72–0.92). Our results indicated that CD may involve different types of pathogenesis and have variable clinical manifestations. In patients with ileal, stenotic or fistulizing CD, the mutant-type rs2043211 polymorphism may generate a potentially protective effect.     

SLC30A8基因多态性与肾移植后糖尿病的相关性

背景：前期研究已经发现,2型糖尿病的易感基因脂联素基因、钙蛋白酶10基因等与中国肾移植患者移植后糖尿病的发生显著相关。猜测其他2型糖尿病的易感基因是否也与移植后糖尿病相关。 目的：分析锌转运蛋白-8(SLC30A8)基因多态性与移植后糖尿病的相关性。 方法：采用实时荧光定量PCR法检测97例移植后糖尿病患者和301例未发生移植后糖尿病的肾移植患者(对照组)的SLC30A8 rs13266634的基因型,采用 logistic 回归分析该基因多态性与移植后糖尿病的相关性。 结果与结论：移植后糖尿病组和对照组患者rs13266634的等位基因频率和基因型分布差异具有显著性意义  (P < 0.05)。用性别、移植时年龄、体质量和体质量指数等危险因素进行校正后,CC基因型患者肾移植后发生移植后糖尿病的风险是TT基因型患者的2.108倍(OR=2.108,95%CI: 1.075-4.131,P=0.044);CC+CT基因型患者肾移植后发生移植后糖尿病的风险是TT基因型患者的1.862倍(OR=1.862,95%CI: 1.049-3.306,P=0.034)。提示SLC30A8基因rs13266634的C等位基因是肾移植后发生移植后糖尿病的独立危险因素。     

The association of endothelin-1 gene polymorphism and its plasma levels with hypertension and coronary atherosclerosis

IntroductionEndothelin-1 (ET-1) is the most potent among all vasoconstrictors, and its association with cardiovascular diseases has been reported before. Our aim was to investigate the association of ET-1 plasma level and its gene polymorphisms (rs5370 and rs10478694) with hypertension and coronary atherosclerosis (CA).Material and methodsThis study was carried out on 128 women and 132 men, who were divided into 4 groups: hypertensive without atherosclerosis (H+A–); hypertensive with atherosclerosis (H+A+); non-hypertensive with atherosclerosis (H–A+); and non-hypertensive without atherosclerosis (control group). Endothelin-1 plasma levels were measured by ELISA, and gene polymorphisms were detected by polymerase chain reaction – restriction fragment length polymorphism (PCR-RFLP) methods. Coronary artery diseases (CAD) were then defined based on angiography data.ResultsThe ET-1 plasma level was significantly higher in the H+A+ group in comparison with the other groups, especially H+A–. Comparing people with CA and those without it, the highest frequency level of the T allele of rs5370 was found in people with CA. Significantly higher frequencies of the 3A allele were detected in hypertensive patients in comparison with non-hypertensive individuals, when analyzing rs10478694.ConclusionsEndothelin-1 plasma level shows a direct association with the risk of CA development. The T allele of rs5370 can be regarded as a risk factor for CA development. The 3A allele of rs10478694 can be associated with the risk of hypertension; therefore, it can be concluded that ET-1 and its gene polymorphisms play an important role in CA development and hypertension observed in the south-eastern populations of Iran.     

Determination of [11C]PBR28 binding potential in vivo: a first human TSPO blocking study

Positron emission tomography (PET) targeting the 18 kDa translocator protein (TSPO) is used to quantify neuroinflammation. Translocator protein is expressed throughout the brain, and therefore a classical reference region approach cannot be used to estimate binding potential (BP_ND). Here, we used blockade of the TSPO radioligand [¹¹C]PBR28 with the TSPO ligand XBD173, to determine the non-displaceable volume of distribution (V_ND), and hence estimate the BP_ND. A total of 26 healthy volunteers, 16 high-affinity binders (HABs) and 10 mixed affinity binders (MABs) underwent a [¹¹C]PBR28 PET scan with arterial sampling. Six of the HABs received oral XBD173 (10 to 90 mg), 2 hours before a repeat scan. In XBD173-dosed subjects, V_ND was estimated via the occupancy plot. Values of BP_ND for all subjects were calculated using this V_ND estimate. Total volume of distribution (V_T) of MABs (2.94±0.31) was lower than V_T of HABs (4.33±0.29) (P<0.005). There was dose-dependent occupancy of TSPO by XBD173 (ED50=0.34±0.13 mg/kg). The occupancy plot provided a V_ND estimate of 1.98 (1.69, 2.26). Based on these V_ND estimates, BP_ND for HABs is approximately twice that of MABs, consistent with predictions from in vitro data. Our estimates of [¹¹C]PBR28 V_ND and hence BP_ND in the healthy human brain are consistent with in vitro predictions. XBD173 blockade provides a practical means of estimating V_ND for TSPO targeting radioligands.