HLA‐G 14‐bp polymorphism: a possible marker of systemic treatment response in psoriasis vulgaris? Preliminary results of a retrospective study

Human leukocyte antigen‐G (HLA‐G) is a nonclassical HLA class I molecule that exerts an immunosuppressive function. A 14‐base pair (bp) sequence insertion/deletion (INS/DEL) polymorphism in the exon 8 at the 3′ untranslated region (UTR) modifies mRNA stability and protein production and has been shown to concur with efficacy of pharmacological treatments in immune‐mediated conditions. The aim of this study was to assess for the first time the correlation between HLA‐G 14‐bp INS/DEL polymorphism with the response to systemic therapy in psoriatic patients. We retrospectively analyzed the HLA‐G 14‐bp INS/DEL polymorphism of HLA‐G gene in patients with moderate to severe plaque psoriasis: 21 treated with acitretin, 16 with cyclosporine, 11 with anti‐TNF‐α. Patients who reached PASI 75 at weeks 10–16 were considered responders. Among patients treated with acitretin, we observed a significantly increased frequency of the HLA‐G DEL allele and of the DEL/DEL genotype in responder patients when compared with nonresponders. An association between HLA‐G genotype and response to cyclosporine and biologics was not found. The significant association between HLA‐G 14‐bp DEL allele and 14‐bp DEL/DEL genotype and acitretin clinical outcome may suggest an advantage of this allele and propose this HLA‐G polymorphism as a potential marker of response to acitretin in psoriatic patients.     

Association of MB-COMT polymorphisms with schizophrenia-susceptibility and symptom severity in an African cohort

The catechol-O-methyltransferase (COMT) gene is an attractive schizophrenia candidate gene, encoding a catabolic dopamine enzyme. The enzyme exists as two distinct isoforms, with the membrane bound enzyme (i.e. MB-COMT) being predominantly expressed in the brain. Since African populations remain underrepresented in genetic/genomic research, we performed an association study to determine whether MB-COMT genetic variants are associated with schizophrenia-susceptibility and symptom severity in the South African Xhosa population. Fourteen candidate polymorphisms were selected by means of a literature search and in silico analyses and were subsequently genotyped in a cohort of 238 Xhosa schizophrenia patients and 240 healthy Xhosa controls. Genetic association was tested with schizophrenia-susceptibility as well as symptom severity within the patient group. Polymorphisms of interest were also analysed using functional assays. Two SNPs, rs2020917 (OR=0.54, 95% CI 0.37-0.79; P=0.0011) and rs737865 (OR=0.52, 95% CI 0.36-0.74; P=0.0002), in the P2 promoter region were significantly associated with schizophrenia as well as an increase (increase=11.2%, 95% CI 3.7%-19.2%; P=0.0031) in reporter gene expression. The minor alleles of these SNPs were underrepresented in the schizophrenia cohort, indicating a possible protective effect. The P2 region also formed part of a haplotype found to be associated with the severity of the negative symptoms of the disorder. The data generated by this study indicate that genetic variation of MB-COMT could be associated with schizophrenia and negative symptom severity in the Xhosa population and may therefore be one of the genomic loci contributing towards the disorder in the South African community. Future large-scale studies in other African schizophrenia populations are required to further elucidate the significance of these findings.     

The association of 5-HTR2A-1438A/G, COMTVal158Met, MAOA-LPR, DATVNTR and 5-HTTVNTR gene polymorphisms and antisocial personality disorder in male heroin-dependent Chinese subjects

Objective

To explore the association between the 5-HTR2A-1438A/G, COMTVal158Met, MAOA-LPR, DATVNTR and 5-HTTVNTR polymorphisms with comorbidity of antisocial personality disorder in male heroin-dependent patients.

Subjects and methods

In case control study, we compared the polymorphic distributions of 5-HTR2A-1438A/G, COMTVal158Met, MAOA-LPR, DATVNTR and 5-HTTVNTR in 588 male heroin-dependent patients (including 311 patients with antisocial personality disorder and 277 patients without antisocial personality disorder) and 194 normal males by genotypes, alleles, and interaction between genes.

Results

Between male heroin-dependent patients with antisocial personality disorder and normal males, and between male heroin-dependent patients with and without antisocial personality disorder, the distributions of 5-HTTVNTR polymorphic genotypes and alleles were in statistical significance. Individuals carrying 10R allele were in higher risk of the comorbidity of antisocial personality disorder and heroin dependence. By MDR analyses, the interaction between 5-HTTVNTR and DATVNTR was close to statistical significance in predicting the risk of antisocial personality disorder in male heroin dependent patients. In male heroin dependent patients, individuals carrying 5-HTTVNTR 10R allele or/and DATVNTR 9R allele were in higher risks of co-occurring antisocial personality disorder, while individuals with 5-HTTVNTR 12R/12R and DATVNTR 10R/10R genotypes together were in lower risks of antisocial personality disorder.

Conclusion

5-HTTVNTR, and the interaction between 5-HTTVNTR and DATVNTR may be associated with the comorbidity of antisocial personality disorder in male heroin-dependent patients.     

A new method for detection of pandemic influenza virus using High Resolution Melting analysis of the neuraminidase gene

Diagnostic methods based upon exclusive detection of haemagglutinin do not detect sequence variation in other gene segments of the Influenza A virus. A complementary approach is described based upon high-resolution melting curve analysis of the neuraminidase gene, an approach with the potential ability to detect small changes in the neuraminidase sequence without the need for specific probes.     

Thymidylate Synthase Polymorphisms and Risk of Lung Cancer among the Jordanian Population: a Case Control Study

Background: Thymidylate synthase (TS) catalyzes the methylation of deoxyuridylate to deoxythymidylate and is involved in DNA methylation, synthesis and repair. Two common polymorphisms have been reported, tandem repeats in the promoter-enhancer region (TSER), and 6bp ins/del in the 5 UTR, that are implicated in a number of human diseases, including cancer. The association between the two polymorphisms in risk for lung cancer (LC) was here investigated in the Jordanian population. Materials and Methods: An age, gender, and smoking-matched case-control study involving 84 lung cancer cases and 71 controls was conducted. The polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) technique was used to detect the polymorphism of interest. Results: Individuals bearing the ins/ins genotype were 2.5 times more likely to have lung cancer [(95%CI: 0.98-6.37), p=0.051]. Individuals who were less than or equal to 57 years and carrying ins/ins genotype were 4.6 times more susceptible to lung cancer [OR<57 vs >57years: 4.6 (95%CI: 0.93-22.5), p=0.059)]. Genotypes and alleles of TSER were distributed similarly between cases and controls. Weak linkage disequilibrium existed between the two loci of interest (Lewontin’s coefficient [D’]) (LC: D’ =0.03, r2: 0. 001, p= 0.8; Controls: D’ =0.29, r2: 0.08, p=0.02). Carriers of the “3 tandem repeats_insertion” haplotype (3R_ins) were 2 times more likely to have lung cancer [2 (95%CI: 1.13-3.48), p=0.061]. Conclusions: Genetic polymorphism of TS at 3` UTR and its haplotype analysis may modulate the risk of lung cancer in Jordanians. The 6bp ins/del polymorphism of TS at 3 `UTR is more informative than TSER polymorphism in predicting increased risk.     

多巴胺D4受体基因exon Ⅲ 48bp VNTR多态性与学龄儿童气质的相关性

目的 了解多巴胺D4受体基因（DRD4）第3外显子48bp可变串联重复序列多态性（exon Ⅲ 48bp VNTR）与学龄儿童气质的相关性。方法 随机整群抽取350名8~12岁健康儿童进行问卷调查,其中一半儿童进行口腔上皮采集,其中164名儿童问卷资料完整且口腔上皮细胞中DNA浓度较高的样本纳入研究,运用PCR技术进行DRD4 exon Ⅲ 48bp VNTR分型,并分析该基因及其与环境的交互作用对气质的影响。结果 携带L-DRD4基因型儿童在活动水平、反应强度、情绪本质以及坚持性4个维度的得分均低于S-DRD4基因型儿童（P < 0.05）。母亲教养方式为拒绝/否认（OR=2.281,P < 0.05）、儿童性别（OR=2.766,P < 0.05）的主效应及儿童性别与DRD4 exon Ⅲ 48bp VNTR的交互作用对儿童活动水平有影响（OR=0.582,P < 0.05）。DRD4 exon Ⅲ 48bp VNTR主效应（OR=0.314,P < 0.01）及该基因与母亲教养方式为拒绝/否认的交互作用（OR=1.872,P < 0.01）对儿童反应强度有影响。DRD4 exon Ⅲ 48bp VNTR （OR=0.420,P < 0.05）及母亲教养方式为拒绝/否认（OR=2.236,P < 0.05）的主效应对儿童坚持性有影响。结论 DRD4 exon Ⅲ 48bp VNTR及该基因与其他因素的交互作用可能影响学龄儿童的活动水平和反应强度。     

Array comparative genomic hybridization (aCGH) reveals the largest novel deletion in PCCA found in a Saudi family with propionic acidemia

Propionic acidemia is a metabolic disorder (OMIM 606054) caused by deficiency of the propionyl-coenzyme A (CoA) carboxylase, which subsequently results in accumulation of propionic acid. Patients may initially present with poor feeding, vomiting, loss of appetite, hypotonia, and lethargy. Later, most children will show different degrees of motor, social and language delay even more serious medical problems, including heart abnormalities, seizures, coma, and possibly death. Two siblings affected with propionic acidemia were screened for putative mutations in PCCA and PCCB genes coding α and β subunits of propionyl-coenzyme A (CoA) carboxylase, respectively. Both patients had a mild–severe form of propionic acidemia. The investigations using PCR, long-PCR, array comparative genomic hybridization (aCGH), and sequencing techniques showed a 73 kb deletion extending from intron 16 to intron 19 and an 18 bp insertion at the distal end of the deletion in PCCA gene. The deletion so far is the largest gross change reported in the literature for the PCCA gene.