Association of high-sensitivity C-reactive protein with susceptibility to Schizophrenia in Tunisian population

The pathogenic mechanisms underlying Schizophrenia (SZ), one of the most frequent mental disorders, are complex and poorly understood. Several evidences suggest that inflammatory processes may underpin some of its neurobiological correlates. The aim of this study was: (i) to analyze the potential association between circulating levels of the C-reactive protein (CRP), a crucial inflammatory marker, and Schizophrenia in Tunisian patients and healthy controls (HC) cohorts; (ii) to investigate the genetic diversity of three CRP variants (rs1417938, rs1130864 and rs1205) and; (iii) to analyze a potential relationship between expression and genetic data and clinical and socio demographical characteristics. CRP polymorphisms were exanimated for 155 patients and 203 HC by taqMan5′-nuclease. High-sensitivity CRP (hs-CRP) serum level was measured in 128 clinically stable out-patient SZ patients and 63 HC subjects via an automated biochemical analyzer. We found that hs-CRP levels were significantly higher in SZ patients as compared to HC. No significant differences were found when the proportions of CRP variants were compared in patients and HC. Further analysis according to clinical and socio demographical characteristics revealed a positive association with age and hypertension. Our data on an original Tunisian sample confirm the previous finding in others population groups.     

RAD23B基因rs10759225位点多态性与含铂类方案治疗非小细胞肺癌疗效和血液学毒性的关系

目的 探讨RAD23B基因rs10759225位点多态性与含铂类方案一线治疗中晚期非小细胞肺癌（non-small cell lung cancer，NSCLC）的疗效及血液学毒性的关系。方法 回顾性收集接受含铂类联合方案一线治疗的150例NSCLC患者的临床资料及外周血样本，采用改良多重高温连接酶检测反应技术对rs10759225进行基因分型，并分析其与患者疗效及血液学毒性的关系。结果 150例NSCLC患者的总有效率（ORR）为28.7%（43/150）。与携带G/G基因型患者比较，携带A等位基因型（G/A和A/A）患者接受含铂类方案治疗的ORR显著提高（OR_校正=1.780，95%CI：1.110~2.884，P=0.042）。全组患者中位无进展生存期（mPFS）为5.6个月，各基因型患者的mPFS差异均无统计学意义（P>0.05）。以G/G基因型为参照，A/A基因型与患者化疗后发生Ⅲ/Ⅳ度白细胞减少的风险相关（OR_校正=0.468，95%CI：0.204~0.711，P=0.008）；A等位基因型分别与患者发生Ⅲ/Ⅳ度中性粒细胞减少（OR_校正=0.502，95%CI：0.155~0.887，P=0.022）和≥Ⅰ度血小板减少的风险有关（OR_校正=0.494，95%CI：0.101~0.833，P=0.047）；而G/A基因型与患者发生Ⅱ/Ⅲ度贫血的风险有关（OR_校正=0.504，95%CI：0.213~0.890，P=0.047）。结论 RAD23B基因rs10759225位点多态性与含铂类方案治疗NSCLC的疗效及血液学毒性有关，但与患者的预后无关。与携带G/G基因型患者比较，携带A等位基因型患者的疗效更好，但发生骨髓抑制的风险更高。     

Human leukocyte antigen polymorphisms and Kaposi's sarcoma-associated herpesvirus infection outcomes: A call for deeper exploration

Host genetic background may influence the immunity to resist viral infection. As the most polymorphic loci in the entire human genome, the human leukocyte antigen (HLA) system plays an important role in innate and adaptive immune responses to many invading pathogens. Studies have shown that an association might exist between HLA polymorphisms and susceptibility to Kaposi's sarcoma-associated herpesvirus (KSHV) infection and associated diseases. However, discrepant conclusions were reached among different subjects with different detection methods. Therefore, it is now urgent to summarize current results and figure out the achievements and deficiencies of the existing research for the reference to future studies. A better understanding about the role of HLA polymorphisms in KSHV infection outcome would enable us to elucidate the pathways through which the virus evades the host defense system and improve strategies for the prevention and treatment of KSHV infection.     

Association of ficolin‐1 and ficolin‐3 gene variation and pulmonary tuberculosis susceptibility in a Chinese population

BackgroundThe aim of our study was to estimate the association of ficolin‐1 (FCN1) gene (rs10120023, rs1071583) and ficolin‐3 (FCN3) gene (rs3813800, rs10794501) polymorphisms and pulmonary tuberculosis (PTB) susceptibility, as well as their several clinical features, in a Chinese population.MethodsThis study included a cohort of 489 PTB patients and 489 healthy controls, and the four SNPs were genotyped by improved multiple ligase detection reaction (iMLDR).ResultsWe found that there were no significant differences regarding the allele and genotype frequencies of FCN1 rs10120023, rs1071583 and FCN3 rs3813800, rs10794501 between PTB patients and healthy controls (all p > 0.05). The association of three main haplotypes (CC, CT, and TC) in FCN1 and three main haplotypes (CT, GA, and GT) in FCN3 with PTB susceptibility was also analyzed, and no significant association was detected (all p > 0.05). In FCN1, the rs1071583 TT genotype was significantly associated with the occurrence of drug resistance in PTB patients (p = 0.040). In addition, the GG genotype and G allele frequencies of rs3813800 in FCN3 gene were significantly higher in PTB patients with pulmonary infection (p = 0.027, p = 0.020, respectively).Conclusions FCN1 and FCN3 genetic variation were not contributed to the pathogenesis of PTB in Chinese. While rs1071583 and rs3813800 variant might associate with several clinical characteristics of PTB.     

Forensic genetic polymorphisms of 16 X-STR loci in the Yunnan Miao population and their relationship to other Chinese groups

Allele frequencies for 16 X-chromosomal STR (X-STR) loci were obtained from a sample set of 440 unrelated Yunnan Miao individuals in China. A total of 117 alleles were observed in this group, with allele frequencies ranging from 0.0016 to 0.7565. The most informative marker for the studied population was DXS10134, with a polymorphism information content (PIC) of 0.8499, and the least polymorphic locus was DXS6810 (PIC = 0.3071). The power of discrimination (PD) varied from 0.4046 (DXS6800) to 0.8642 (DXS10134) in males and from 0.6188 (DXS6800) to 0.9673 (DXS10134) in females. The combined PDM and PDF were 0.999999989975990 and 0.999999999999949, respectively. The combined MECD and MECT were 0.999983301904059 and 0.999999915883733, respectively. Furthermore, population genetic structure investigation between the Yunnan Miao and 20 other populations using principal component analysis (PCA), multidimensional scaling plot (MDS), and neighboring-joining (NJ) phylogenetic tree analyses illustrated significant genetic difference between the Yunnan Miao and the other populations. This study is the first to provide X chromosome genetic polymorphism data of the Miao population in Yunnan Province and can be used as a supplementary reference to enrich the national database.     

CYP3A5*3基因多态性与晚期非小细胞肺癌患者应用多西他赛的疗效及安全性分析

目的:研究CYP3A5*3基因多态性对应用多西他赛治疗的晚期非小细胞肺癌患者的疗效以及安全性的相关性分析。方法:通过多基因检测技术明确患者CYP3A5*3的基因多态性状态，通过查阅随访表、病理以及随访电话明确患者的基本信息，包括性别、年龄、是否吸烟、EGFR状态和ECOG评分等，明确生存信息，即无进展生存期（PFS）和总生存期（OS）。通过不良反应表统计不良反应发生情况。用卡方检验对基因多态性与患者的不良反应进行相关性分析，用Kaplan-Meier生存曲线分析基因多态性与患者的PFS和OS的关系。结果:在生存分析方面，CYP3A5*3纯合突变型患者的中位总生存期约26个月，高于杂合型的24个月和野生型的22个月（P=0.833）。CYP3A5*3纯合突变型患者的中位无进展生存期4个月，也高于杂合型的2个月和野生型的3个月（P=0.306）。在不良反应方面，共有11例患者发生Ⅲ级以上骨髓抑制，其中7例（63.6%）患者为CYP3A5*3纯合突变型，考虑该基因型发生中重度骨髓抑制的可能性更大（P=0.415）。此外，有6例患者发生皮疹，其中5例（83.3%）为CYP3A5*3纯合突变型，还包括1例Ⅲ度皮疹。考虑该基因型患者发生皮疹的可能性更大（P=0.490）。手足综合征、神经毒性、肾毒性以及口腔黏膜炎等仅发生在 CYP3A5*3野生型及CYP3A5*3纯合突变型患者中。结论:应用多西他赛的晚期非小细胞肺癌患者中，CYP3A5*3纯合突变型患者的生存期高于杂合型和野生型患者。CYP3A5*3纯合突变型患者发生中重度骨髓抑制、皮疹的风险可能性更大。     

Association of interleukin-6 gene polymorphisms with the risk of hepatocellular carcinoma: An up-to-date meta-analysis

Background:This study was aimed to evaluate the association between interleukin-6 (IL-6) gene polymorphisms and the risk of hepatocellular carcinoma (HCC) in a meta-analysis.Methods:A literature search was performed for case-control studies published during May, 1993 to May, 2020 focusing on IL-6 gene polymorphisms (–174G > C, –572G > C, and –597G > A) and HCC susceptibility by using PubMed, Cochrane Database, EMBASE, Web of science, and China National Knowledge Infrastructure. From 128 full-text articles, 11 were included in this meta-analysis. I² index was used to assess heterogeneity and Newcastle-Ottawa Scale was utilized for quality assessment.Results:For IL-6 –174G > C polymorphism, in codominant (GG vs CC: odds ratios [OR] = 2.78, 95% confidence intervals [CI] = 1.25–6.19, P = .01, I² = 16%) and recessive (GG+GC vs CC: OR = 2.76, 95% CI = 1.29–5.90, P = .009, I² = 3%) models, IL-6 –174G>C polymorphism was significantly associated with the risk of HCC. In dominant (GG vs CC+GC: OR = 1.80, 95% CI = 0.92–3.54, P = .09, I² = 86%) and allele (G vs C: OR = 1.49, 95% CI = 0.95–2.32, P = .08, I² = 68%) models, IL-6 –174G>C polymorphism had no impact on the risk of HCC. However, in non-Italian Caucasian population, IL-6 –174G>C polymorphism was significantly related to the occurrence of HCC in both dominant (GG vs CC+GC: OR = 3.26, 95% CI = 2.29–4.65, P < .00001, I² = 0%) and allele (G vs C: OR = 2.48, 95% CI = 1.48–4.15, P = .0006) models. Such correlations also could be observed when healthy individuals were selected as controls. For IL-6 –572G>C and –597G>A polymorphisms, no significant association was observed in all models, regardless of the source of control and population subgroups. No publication bias could be calculated when Begg and Egger tests were employed.Conclusion:This meta-analysis indicated that IL-6 –174G>C polymorphism was significantly related with the risk for HCC, especially in non-Italian Caucasian population. No significant association was observed for the correlation between IL-6 –572G>C and –597G>A polymorphisms and HCC susceptibility.