Polymorphism In Promoter Region Research Articles

The effects of 5-HTTLPR/rs25531 serotonin transporter gene polymorphisms on antisocial personality disorder among criminals in a sample of the Turkish population.

Antisocial personality disorder (ASPD) is a cluster B personality disorder characterized by a disposition for criminal behaviors. It has been determined by previous studies that ASPD may have a genetic origin and the human serotonin transporter gene (SLC6A4) is one of the two serotonergic genes expected to be associated with this disorder. 5-HTT-linked polymorphic promoter region (5-HTTLPR) is a degenerate repeat polymorphic region in SLC6A4, the gene that codes for the serotonin transporter. Among many polymorphisms in SLC6A4, 5-HTTLPR an insertion/deletion (indel) polymorphism and rs25531 single nucleotide polymorphism (SNP) in the 5-HTTLPR polymorphic region contribute to the regulation of SLC6A4 expression. In this study, we aimed to reveal the relationship between frequencies of 5-HTTLPR variants and ASPD among criminals in the Turkish population. Moreover, it was also attempted to figure out the SLC6A4 gene expression level differences regarding these polymorphisms. The 5-HTTLPR/rs25531 genotypes were determined by PCR and restriction length polymorphism (RFLP) analyses and quantitative real-time-PCR was done for measuring the gene expression levels in the case and control groups. Although no significant difference was observed in the distributions of the 5-HTTLPR/rs25531 polymorphisms between the case and control groups, SLC6A4 expression level in the control group was found significantly higher than the case group (p < 0.0001). There was also no significant difference between genotypes in terms of mRNA expression levels in either the control or the case group. According to our results, ASPD in Turkish society is associated with the SLC6A4 gene expression levels, though the distributions of 5-HTTLPR polymorphisms are not different. This study sheds light on future relevant studies as the first study which is conducted in criminals with ASPD in the Turkish community.

A preliminary study of cytokine gene polymorphism effects on Saudi patients with colorectal cancer.

Objectives:To determine the possible associations of polymorphisms in interleukin (IL)-8 (rs4073 T/A), IL-10 (rs1800896 A/G), IL-22 (rs1179251 C/G and rs2227485 C/T), IL-27 (rs17855750 T/G), and transforming growth factor beta 1 (TGFß1) (rs1800469 C/T) with colorectal cancer (CRC) susceptibility in Saudi patients.Methods:The case-control study was carried out between July 2019 and January 2020 in King Khaled University Hospital, Riyadh, Saudi Arabia. A total of 70 patients with CRC and 70 healthy controls were included in the study. Single nucleotide polymorphisms of promoter regions were determined using TaqMan genotyping assays.Results:A statistically significant reduction in CRC risk was identified for carriers of the IL-10 (rs1800896 A/G) AG genotype, IL-22 (rs1179251 C/G) G allele, IL-27 (rs17855750 T/G) G allele and TGFß1 (rs1800469 C/T) CT and TT genotype. While IL-10 (rs1800896 A/G) AA genotype and TGFß1 (rs1800469 C/T) CC genotype were significantly associated with increased susceptibility to CRC. No significant associations were identified between the cytokine polymorphisms of IL-8 (rs4073 T/A) and IL-22 (rs2227485 C/T), and CRC risk.Conclusion:Our findings indicate a significant impact of IL-10 (rs1800896 A/G), IL-22 (rs1179251 C/G), IL-27 (rs17855750 T/G) and TGF-ß1 (rs1800469 C/T) polymorphisms on risk of CRC; while the IL-8 (rs4073 T/A) and IL-22 (rs2227485 C/T) and polymorphisms were not associated with CRC risk.

A functional mutation in the AMPD1 promoter region affects promoter activity and breast meat freshness in chicken.

Freshness is an important index to determine the quality deterioration (protein degradation and changes in appearance) of chilled chicken meat and is a primary consideration of consumers. Adenosine monophosphate deaminase 1 (AMPD1) catalyzes the deamination of adenosine monophosphate to inosine monophosphate in skeletal muscle and is the rate-limiting step in the purine nucleotide cycle. Inosine monophosphate is regarded as an important indicator of meat freshness in chicken. This study investigated the association of polymorphisms in the chicken AMPD1 promoter region with meat freshness during freezing storage. An SNP (c. -905G>A) was found to be associated with the freshness (K-value) of chicken breast meat. Chickens with the AA genotype had significantly lower K-values than those with GG and AG genotypes (P<0.01). Individuals with the AA genotype also had higher breast meat AMPD1 mRNA levels than did those with the GG and AG genotypes (P<0.01, P<0.05). A luciferase assay revealed that genotype AA had greater transcriptional activity than genotype GG. Transcription factor binding site analysis identified distinct putative transcription factor binding sites in the two alleles of mutation site c. -905. In summary, we identified an SNP (c. -905G>A) in the promoter region of the AMPD1 gene that may modulate the binding affinity of different transcription factors to control AMPD1 expression and affect the freshness K-value of chicken meat.

Global distribution, dissemination and overexpression of potent multidrug efflux pump RE-CmeABC in Campylobacter jejuni.

To investigate the global distribution, dissemination and overexpression of RE-CmeABC in Campylobacter jejuni. WGS information for 433 RE-cmeABC-positive C. jejuni isolates (including 18 isolates sequenced in this study and 415 isolates from GenBank) was used for the generation of minimum-spanning trees with STs. WGS information for 95 representative RE-cmeABC-positive C. jejuni isolates was used for phylogenetic analysis. RT-PCR was conducted to evaluate the association between inverted repeat (IR) sequence diversity in the RE-CmeABC promoter region and RE-cmeABC gene expression. WGS analysis revealed the global distribution of RE-cmeABC among C. jejuni from more than 10 countries. MLST results indicated that various STs were involved in the dissemination of RE-cmeABC, with ST2109 being the most predominant ST. Phylogenetic analysis revealed the close relationship between RE-cmeABC-carrying C. jejuni isolates from poultry and humans. The IR polymorphism in the RE-CmeABC promoter region is associated with the overexpression of RE-cmeABC, which was demonstrated experimentally by RT-PCR. To the best of our knowledge, our analysis represents the first view of the global distribution of RE-CmeABC, which is horizontally transferable and diffused regionally in a clonal manner. The close relationship of RE-cmeABC-positive C. jejuni from poultry and humans supports the potential of these isolates for zoonotic transmission. Overexpressed RE-CmeABC in C. jejuni will increase the fitness of the corresponding bacteria and be of advantage under antimicrobial selection.

Relationship between TIM-3 gene polymorphisms and steroid-resistant primary nephrotic syndrome in children

Nephrotic syndrome, also known as nephrosis, is a collection of symptoms in medicine and urology caused by damage to the basement membrane of the kidney glomeruli and the kidneys excrete a large amount of protein. This experiment was carried out to investigate the association of three single nucleotide polymorphisms (SNPs) of T-cell immunoglobulin and mucin-domain-containing-3 (Tim-3) with childhood primary nephrotic syndrome (PNS) steroid response in Han Chinese. For this purpose, a total of 218 children with steroid-resistant PNS and 189 children with steroid-responsive PNS were enrolled in this case-control study. Three single nucleotide polymorphisms (SNPs) of the TIM-3 gene promoter region (rs4704853, rs1051746, and rs10053538) were analyzed by polymerase chain reaction (PCR) and restriction enzyme digestion. Results showed that there were 124 males and 94 females in the steroid-resistant PNS group and 114 males and 75 females in the steroid-responsive PNS group. The mean ages of the two groups were 7.9 years and 7.7 years, respectively. The distribution of alleles of Rs1051746 and Rs10053538 were significantly different between the steroid-resistant PNS group and the steroid-responsive PNS group (P-value = 0.047 and 0.012, respectively). The distribution of their genotypes was also significantly different between the steroid-resistant PNS group and the steroid-responsive PNS group (P-value = 0.044 and 0.010, respectively). Haplotype G-C-G was less frequent among steroid-resistant PNS children than the steroid-responsive PNS children (P = 0.015). There was no significant difference between the three SNPs of TIM-3 and the clinical features of these PNS children (P&gt;0.05). It concluded that this study provided evidence showing that the polymorphisms of Rs1051746 and Rs10053538 at the TIM-3 gene were related to childhood PNS steroid response. This result provided fundamental support for future studies on the role of TIM-3 in pathogenesis and therapy of childhood PNS.

Threat-Avoidance Tendencies Moderate the Link Between Serotonin Transporter Genetic Variation and Reactive Aggression.

The short (S) allele of the serotonin transporter-linked promoter region (5-HTTLPR) polymorphism has been linked to reactive aggression in men, but this association is less consistent in females. Reactive aggression has been particularly described as a result of fear-driven defense to threat, but how this interaction between defensive behavior and aggression is expressed in S-allele carriers remains unknown. In order to explore this interplay between 5-HTTLPR genotype, defensive behavior and reactive aggression, we combined genotyping with objective measures of action tendencies toward angry faces in an approach-avoidance task (AAT) and reactive aggression in the Taylor aggression paradigm (TAP) in healthy females, N = 95. This study shows that female S-allele carriers in general display increased implicit reactive aggression (administering aversive white noise) toward opponents. Furthermore, we found that threat-avoidance tendencies moderate the association between 5-HTTLPR genotype and aggression displayed on the TAP. Together, these findings indicate a positive correlation between avoidance of angry faces in the AAT and reactive aggression in the TAP exclusively present in S-allele carriers.

MiR-215 Targeting Novel Genes EREG, NIPAL1 and PTPRU Regulates the Resistance to E.coli F18 in Piglets

Previous research has revealed that miR-215 might be an important miRNA regulating weaned piglets’ resistance to Escherichia coli (E. coli) F18. In this study, target genes of miR-215 were identified by RNA-seq, bioinformatics analysis and dual luciferase detection. The relationship between target genes and E. coli infection was explored by RNAi technology, combined with E. coli stimulation and enzyme linked immunosorbent assay (ELISA) detection. Molecular regulating mechanisms of target genes expression were analyzed by methylation detection of promoter regions and dual luciferase activity assay of single nucleotide polymorphisms (SNPs) in core promoter regions. The results showed that miR-215 could target EREG, NIPAL1 and PTPRU genes. Expression levels of three genes in porcine intestinal epithelial cells (IPEC-J2) in the RNAi group were significantly lower than those in the negative control pGMLV vector (pGMLV-NC) group after E. coli F18 stimulation, while cytokines levels of TNF-α and IL-1β in the RNAi group were significantly higher than in the pGMLV-NC group. Variant sites in the promoter region of three genes could affect their promoter activities. These results suggested that miR-215 could regulate weaned piglets’ resistance to E. coli F18 by targeting EREG, NIPAL1 and PTPRU genes. This study is the first to annotate new biological functions of EREG, NIPAL1 and PTPRU genes in pigs, and provides a new experimental basis and reference for the research of piglets disease-resistance breeding.

Significant associations between 5-hydroxytryptaminetransporter-linked promoter region polymorphisms of the serotonin transporter (solute carrier family 6 member 4) gene and Thai patients with autism spectrum disorder.

Autism spectrum disorder (ASD) is a form of pervasive developmental disorder manifested by impairment in social interactions and repetitive behaviors. Although genetic contribution is strongly suspected in autism, the specific genetic factors remain unidentified. Hyperserotoninemia has been reported in some autistic patients, and several studies have demonstrated an association between 5-hydroxytryptamine-transporter-linked promoter region (5-HTTLPR) polymorphisms and rs25531 single nucleotide polymorphism in the serotonin transporter gene (solute carrier family 6 member 4; SLC6A4) and ASD, indicating a possible involvement of the serotonin system in the etiology of ASD.To explore this situation further, a case-control association study of 5-HTTLPR and rs25531 polymorphisms on Thai ASD patients was conducted. A total of 188 ASD cases fulfilling the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria (156 males and 32 females) and a total of 250 normal controls were recruited from the same ethnic backgrounds. 5-HTTLPR polymorphisms (Long, L; Short, S) and rs25531 (A/G) single nucleotide polymorphism were genotyped and compared between the patients and normal controls using chi-square statistics.The L/L genotype was more common in patients than in the controls (13.8% vs 5.2%, P = .006), and the LA haplotype was found in patients more than the controls (16.9% vs 12.2%, P = .048). When male patients were analyzed alone (156 individuals), the associations were also statistically significant with P = .017 for L/L genotype, and P = .019 for LA haplotype distribution.Our findings support previous reports suggesting an association between the 5-HTTLPR and rs25531 polymorphisms of SLC6A4 and patients with ASD.

Interleukin-10 and tumour necrosis factor alpha promoter region polymorphisms and susceptibility to urogenital schistosomiasis in young Zimbabwean children living in Schistosoma haematobium endemic regions.

BackgroundHost genetic factors can influence susceptibility, morbidity and mortality from schistosomiasis. The study explored the association between single nucleotide polymorphisms (SNPs) in interleukin-10 (IL-10) and tumour necrosis factor alpha (TNF-α) promoter regions and susceptibility to Schistosoma haematobium infection.MethodsUrine specimens were collected from 361 primary school children aged 5–15 years from schistosomiasis endemic areas of Manicaland and Mashonaland central provinces. Schistosoma haematobium was diagnosed using the urine filtration method. Only 272 participants provided adequate blood for genotyping. Genotyping was performed using the amplification refractory mutation system-polymerase chain reaction. The association between IL-10 and TNF-α SNPs and S. haematobium infection was analysed using the chi-square test.ResultsSchistosoma haematobium infection was confirmed in 26.8% of the participants. No significant difference in S. haematobium prevalence between men (51.6% of those infected) and women (48.4%) (χ2 = 0.008, df = 1, p = 0.928) was observed. The total IL-10 -1082 G, IL-10 -819 C and TNF-α -308G allele distribution between S. haematobium infected and uninfected participants was 50.7% and 51.5% (χ2 = 0.025, df = 1, p = 0.87), 54.3% and 60.6% (χ2 = 1.187, df = 1, p = 0.187) and 82.1% and 80.9% (χ2 = 0.099, df = 1, p = 0.753), respectively, and the differences were not significant.ConclusionInterleukin-10 -1082 G/A, IL-10 -819 C/T and TNF-α -308 G/A SNPs were not significantly associated with susceptibility to S. haematobium infection. The prevalence of schistosomiasis is still in the moderate range and is similar in boys and girls.

ALL-232: Genetic Variants of Tumor Necrosis Factor α and Interleukin-10 in Childhood and Adult Acute Lymphoblastic Leukemia

Context Interleukin-(IL)10 and tumor necrosis factor (TNF) a have a significant role in malignancies. Genes encoding these cytokines are linked with different levels of gene transcription. Objective Analyzing IL-10 and TNFα gene polymorphisms and their contribution to ALL prognosis and survival. Design This prospective observational study was conducted from June 2017 until Oct 2019. Setting Oncology Center Mansoura University, Egypt. Patients or other participants We genotyped 64 children and 76 adult ALL patients for IL-10-1082A > G and TNFα-308G > A polymorphisms in the gene promoter region. We used polymerase chain reaction (restriction fragment length polymorphism method) for the molecular analysis. Results Pediatric ALL patients showed TNFα A allele and IL-10 A allele, which were associated with older age (p = 0.04, 0.03), extramedullary disease (p = 0.04, 0.001), and carried Philadelphia chromosome (p = 0.02, 0.001), compared to the G allele, respectively. IL-10-1082AA and TNF 308AA genotypes carried on the Ph-positive chromosome were associated with a longer time to CR and a higher rate of relapse than other genotypes. The IL-10 (GG) genotype was associated with significant improvement of OS compared to IL-10 (GA) and (AA) genotypes (p = 0.026). The adult ALL patients carrying the A allele of TNFα had a higher rate extramedullary disease (p = 0.009) and a higher rate of relapse (p = 0.003). Also, we found increased frequency of the IL-10-A allele with advanced age (p = 0.03), lower Hb level (p = 0.04), increased extramedullary disease (p = 0.001), and Ph chromosome positivity (p = 0.001), which resulted in longer time to CR (p = 0.003) and high relapse rate (p = 0.002). IL-10 (AA) and TNFα (AA) genotype patients were associated with extramedullary disease, carried the Ph-positive chromosomal abnormality, and had a higher rate of relapse than other genotypes among adult ALL patients. Patients with IL-10 (GG) and TNFα (GG) genotypes did not show significant improvement of OS and RFS by Kaplan-Meier curves (p > 0.05) compared to other genotypes. Conclusion IL-10 (AA) and TNFα (AA) were associated with poor prognostic factors in childhood and adulthood ALL. This might modulate the risk, overall survival, and relapse-free survival among ALL patients.

Association of polymorphism c.-124G>A and c.-16 C>T in the promoter region of human INHA gene with altered sperm parameters; A pilot study.

The objective of this was to demonstrate the association of Inhibin α (INHα) c.-124G>A and INHα-c.-16 C>T polymorphisms with altered sperm parameters in a selected male population of Karachi, Pakistan. In this pilot study, male subjects were stratified on the basis of the WHO criteria for altered sperm parameters; 83 (cases-altered sperm parameters) and 30 (controls-normal sperm parameters) subjects were included for analysis of INHα-c.124G>A polymorphism and 88 (cases) and 38 (controls) were analysed for INHα -c-16 C>T polymorphism. Genotyping of INHα-c.-124G>A and INHα-c.-16 C>T was performed by PCR-RFLP, genotype distribution in Hardy-Weinberg equilibrium was evaluated by binary logistic regression model. For the c.-124G>A polymorphism in INHα gene, frequency of the three major genotypes in controls was: GG: 80.0%, GA: 20.0% and AA: 0% and in cases was: GG: 59.0%, GA: 30.2% and AA: 10.8%. The GG genotype was significantly associated with male infertility (P < .045, OR = 2.776, 95% CI = 1.025-7.513) while the GA genotype was not significantly associated with infertility (P < .290 OR = 0.580, 95% CI = 0.211-1.593). Frequency of mutant AA genotype was 10.8% in cases (altered sperm parameters) and absent (0%) in normal sperm parameter (controls). The frequencies of three major genotypes CC, CT and TT did not show any significant difference between cases and controls (P > .05). The results from our study exhibited a significant association of c.-124G>A polymorphism in the INHα gene promoter region with male infertility in the Pakistani population. A significant association of c.-16 C>T polymorphism with male infertility, however, was not observed. Further large-scale studies should be conducted to confirm this association.

Genetic Polymorphism of the Nrf2 Promoter Region (rs35652124) Is Associated with the Risk of Diabetic Foot Ulcers.

The genetic polymorphism in the nuclear factor erythroid 2-related factor 2 (Nrf2) gene has been reported as one of the prognosis markers for various diseases, including cancer. Nrf2 is a key transcription factor involved in wound healing by regulating angiogenesis. We investigated the genetic association of NRF2 single-nucleotide polymorphism rs35652124 with T2DM and DFU and assessed its functional impact. A total of 400 subjects were recruited for the study and categorized into three groups: infected DFU patients (DFU, n = 100), T2DM patients without complications (T2DM, n = 150), and healthy adults with normal glucose tolerance (NGT, n = 150). The subjects were genotyped by PCR-RFLP, and the polymorphism was identified by bidirectional Sanger sequencing. The expression of NRF2, IL-10, TNF-α, and IL-6 was studied by qPCR to evaluate the functional impact of rs35652124. The “TT” genotype of rs35652124 was associated with a significant risk for T2DM [OR = 2.2 (1.2-4.2), p = 0.01] and DFU [OR = 7.9 (4-14.9), p < 0.0001]. A significant decrease in transcriptional levels of NRF2 and IL-10 and a remarkable increase in TNF-α and IL-6 were observed in subjects with TT genotype. In conclusion, rs35652124 (TT) is a harmful genetic variant that predisposes to insulin resistance and impaired angiogenesis. Hence, it may serve as a diagnostic genetic marker for T2DM and DFU in combination with different inflammatory markers.

Prevalence of UGT1A1 (TA)n promoter polymorphism in Panamanians neonates with G6PD deficiency

A relationship between the polymorphism in promoter region of the UGT1A1 gene and the development of jaundice has been demonstrated recently. This polymorphism leads to 30% of normal rate transcription initiation of UGT1A1 gene, thus decreasing the bilirubin glucuronidation. The combination of the G6PD deficiency and polymorphism in neonates and adults may causepronounced hyperbilirubinaemias. The aim of this study was to analyse the variations in the UGT1A1 gene promoter in Panamanians neonates with G6PD deficiency and its association with neonatal jaundice (NJ). We identified five different genotypes of TA repeats, in 17 neonates (42.5%) the normal variant TA6/TA6 and in the other 57.5% of the subjects: TA7/TA7 (12.5%), TA6/TA7 (40%), TA6/TA8 (2.5%) and TA6/TA5 (2.5%). Additionally 75% of the 16 newborns that showed NJ had an abnormal variant in the promotersequence, although, there was no significant difference (P = 0.068). The risk of jaundice in neonates with TA7 variant was thrice higher in subjects than with other alleles (P = 0.093, CI: 0.81-11.67). The TA7 allele frequency in this study (0.325) was consistent with the global frequency and similar to Caucasians. The results proved that there is no significant relationship between promoter polymorphism in UGT1A1 and NJ in G6PD deficient Panamanian newborns. Further studies with a greater number of subjects would determine the exact relationship between marked NJ and UGT1A promoter variations.

Germline and Somatic Pharmacogenomics to Refine Rectal Cancer Patients Selection for Neo-Adjuvant Chemoradiotherapy

Neoadjuvant chemoradiotherapy (nCRT) followed by radical surgery is the standard of care for patients with Locally Advanced Rectal Cancer (LARC). Current selection for nCRT is based on clinical criteria regardless of any molecular marker. Pharmacogenomics may be a useful strategy to personalize and optimize nCRT in LARC. This review aims to summarize the most recent and relevant findings about the role of germline and somatic pharmacogenomics in the prediction of nCRT outcome in patients with LARC, discussing the state of the art of their application in the clinical practice. A systematic literature search of the PubMed database was completed to identify relevant English-language papers published up to January 2020. The chemotherapeutic backbone of nCRT is represented by fluoropyrimidines, mainly metabolized by DPD (Dihydro-Pyrimidine Dehydrogenase, DPYD). The clinical impact of testing DPYD*2A, DPYD*13, c.2846A > T and c.1236G > A-HapB3 before a fluoropyrimidines administration to increase treatment safety is widely acknowledged. Other relevant target genes are TYMS (Thymidylate Synthase) and MTHFR (Methylene-Tetrahydro-Folate Reductase), whose polymorphisms were mainly studied as potential markers of treatment efficacy in LARC. A pivotal role of a TYMS polymorphism in the gene promoter region (rs34743033) was reported and was pioneeringly used to guide nCRT treatment in a phase II study. The pharmacogenomic analysis of other pathways mostly involved in the cellular response to radiation damage, as the DNA repair and the activation of the inflammatory cascade, provided less consistent results. A high rate of somatic mutation in genes belonging to PI3K (Phosphatidyl-Inositol 3-Kinase) and MAPK (Mitogen-Activated Protein Kinase) pathways, as BRAF (V-raf murine sarcoma viral oncogene homolog B1), KRAS (Kirsten Rat Sarcoma viral oncogene homolog), NRAS (Neuroblastoma RAS viral (v-ras) oncogene homolog), PIK3CA (Phosphatidyl-Inositol-4,5-bisphosphate 3-Kinase, Catalytic Subunit Alpha), as well as TP53 (Tumor Protein 53) was reported in LARC. Their pharmacogenomic role, already defined in colorectal cancer, is under investigation in LARC with promising results concerning specific somatic mutations in KRAS and TP53, as predictors of tumor response and prognosis. The availability of circulating tumor DNA in plasma may also represent an opportunity to monitor somatic mutations in course of therapy.

Association between 5-hydroxytryptamine transporter gene-linked promoter region polymorphism and the susceptibility of lifelong premature ejaculation: a meta-analysis involving 1,604 subjects.

The relationship between 5-hydroxytryptamine transporter-linked promoter region (5-HTTLPR) gene and lifelong premature ejaculation (LPE) risk was discussed widely for the last few years, which was still controversial and remained to be explored. We performed the meta-analysis with 8 reliable research, which were searched in the following databases: PubMed, Embase and Cochrane Library. We also performed random and fixed effects models to evaluate the odds ratios (ORs) and 95% confidence intervals respectively. By pooling all included studies, we found that SS genotype of 5-HTTLPR polymorphism was linked with significantly higher PE risk in Caucasian population (OR =0.635, 95% CI: 0.417–0.958, I2=0.311, P=0.035), and S-allele of 5-HTTLPR polymorphism increased the risk of LPE significantly in Asian population (OR =0.656, 95% CI: 0.539–0.799, I2=0.435, P<0.001). However, no significant was observed between 5-HTTLPR gene polymorphism and LPE risk in overall studies. Further studies were anticipated to be done.

Meta-analysis of 5-hydroxytryptamine transporter gene promoter region polymorphism and post-stroke depression.

ObjectiveTo investigate the relationship between 5-hydroxytryptamine transporter gene promoter region (5-HTTLPR) gene polymorphism and post-stroke depression (PSD).MethodsWe searched the CNKI, China Science and Technology Journal, China WanFang, PubMed, Embase, and Web of Science databases for studies of the relationship between 5-HTTLPR polymorphism and PSD. Data were evaluated using Stata software.ResultsThe L allele was significantly related to the S allele (OR = 0.57, 95% confidence interval (CI) 0.49–0.65). The dominant genotype LL + LS was related to SS (OR = 0.48, 95%CI 0.39–0.59), the recessive genotype LL was related to LS + SS (OR = 0.39, 95%CI: 0.30–0.51), the homozygous genotype LL was related to SS (OR = 0.24, 95%CI 0.18–0.33), and the heterozygous genotype LS was related to SS (OR = 0.55, 95 CI 0.44–0.68). All the differences were significant. Ethnicity subgroup analysis showed significant differences among the five genotypes in both Asians and Caucasians. Hardy–Weinberg equilibrium (HWE) subgroup analysis showed that, after removal of a non-HWE-conforming control group, all five genotypes were significant and genotypes LL, LS + LL, and LS and L allele had beneficial effects on recovery from PSD.Conclusion5-HTTLPR gene polymorphism is strongly associated with PSD, and the LL, LS + LL, and LS genotypes and L allele may protect against this condition.

Study of the Relationship between Polymorphisms in the IL-8 Gene Promoter Region and Coccidiosis Resistance Index in Jinghai Yellow Chickens.

Interleukin 8 (IL-8) participates in the immune response and has the function of inducing neutrophils to release lysosomal enzymes and eliminate pathogens. This study was to investigate the effect of single nucleotide mutations in the IL-8 gene promoter region on the coccidiosis resistance index. In this study, 180 infected Eimeria tenella (E. tenella) Jinghai yellow chickens were used as experimental samples. DNA sequencing technology was used to detect single nucleotide polymorphisms (SNPs) in the IL-8 gene promoter region. The association between these SNPs and coccidiosis resistance indexes (including superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-PX), catalase (CAT), nitric oxide (NO), interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), IL-8, and interferon-γ (IFN-γ)) were analyzed. Three SNPs (T-550C, G-398T, and T-360C) were detected. Significant associations were found between each genotype at the T-550C site with NO (p-value = 0.006) and IL-8 (p-value = 0.034) indexes. Significant associations were found between each genotype at the G-398T site with SOD (p-value = 0.042), CAT (p-value = 0.049), NO (p-value = 0.008), and IL-2 (p-value = 0.044) indexes. Significant associations were found between each genotype at the T-360C site with SOD (p-value = 0.007), NO (p-value = 0.046), IL-2 (p-value = 0.041), IL-8 (p-value = 0.039), and IFN-γ (p-value = 0.042) indexes. Haplotype analysis showed that multiple indexes of the H1H3 haplotype combination were significantly higher than other haplotype combinations. Therefore, mutation of the IL-8 gene promoter region has a significant regulatory effect on the coccidiosis resistance index, with a change in transcription factor binding potentially altering IL-8 gene expression, thereby further affecting the IL-8 level in plasma. However, the specific mechanism needs further study.

Genotyping of Tumor Necrosis Factor-? in Inflammatory Bowel Iraqi Patients

The TNF-a gene considered as strong candidate for immune modulator and pro inflammatory cytokine responsible for genetic susceptibility of chronic disease such as the initiation and development of inflammatory bowel disease (IBD).The aim of this study is to investigate the genetic polymorphisms of -1031 in TNF-a gene with susceptibility of Iraqi IBD patients Method: The total number of this study 95 blood samples (75 Iraqi IBD patients and 20 from healthy individuals as a control group). The genetic polymorphisms in TNF-a-1031 gene was investigated using restriction fragment length polymorphism (RFLP) and Sanger sequences techniques. Results: The genotype allele frequency of -1031 polymorphism was significantly higher in CD Iraqi patients (P=0.042 , Chi 4.612. OR= 0.72-1.64) ,C allele may be have protective role , whereas the T allele may increase susceptibility to IBD. In conclusion: The TNF-a -1031 gene polymorphisms in promoter region have an important role in the occurrence of inflammatory bowel disease of Iraqi population especially in CD patients although some results didn’t give us a significant differences.It’s possible that C allele may be have protective role , whereas the T allele may increase susceptibility to IBD

A Promoter Polymorphism (Rs57137919) of ABCG1 Gene Influence on Blood Lipoprotein in Chinese Han Population

Adenosine triphosphate-binding cassette subfamily G member 1 (ABCG1) has the function of transporting free intracellular cholesterol to extracellular high-density lipoprotein (HDL) particles, which play a crucial role in atherosclerosis. The goal of this study is to examine the relationship between the polymorphisms of the ABCG1 gene promoter region and ischemic stroke. In the present study, a case-control association study was designed to identify 3 single-nucleotide polymorphisms (SNPs; rs5713919, rs1378577, and rs1893590), which were located in the promoter region of ABCG1 gene by kompetitive allele-specific polymerase chain reaction genotyping approach. The invitro luciferase assay was done to estimate the effect of rs5713919 on gene expression. Finally, the relationships of 3 SNPs of ABCG1 gene with plasma lipids and lipoproteins were investigated in this Chinese cohort. The correlation analysis between lipids and genotypes showed that the rs57137919 locus genotype was significantly associated with HDL cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels (P=0.021 and P=0.017, respectively), and the GA and AA genotypes had higher HDL-C levels than the GG genotype. Our study provides evidence that ABCG1 promoter region polymorphism rs57137919 has an influence on plasma HDL-C and LDL-C levels in Chinese Han population.

PCR- RFLP Polymorphism at Exon 3 and Promoter Region of Prolactin Gene in Gaolao Cattle

The present study was planned to investigate significant polymorphism in exon3 and promoter regions of prolactin gene in Gaolao cattle and its association (if any) with milk components. A total of 50 randomly selected Gaolao cows were genotyped for PRLGI-RsaI and PRLGIII-Tsp45I loci using PCR-RFLP technique. The PRLGI-RsaI locus was polymorphic and PRLGIII-Tsp45I locus was monomorphic indicating genetic variation at PRLGI-RsaI locus in Gaolao cattle. The allele frequency for the PRLA alleles was found 0.933 and for allele PRLB was 0.067 at PRLGI–RsaI locus. The result of analysis variance showed significant (PÂ0.05) effect of AA genotype on fat % as compared to AB genotype; however non-significant effect of these genotypes was found on protein %, SNF % and lactose % which may be due to small sample resulting in higher error variance. The results of present study indicated that identified prolactin gene polymorphism at PRLGI-RsaI in exon 3 after validation in large breeding populations having precise data records may prove as important candidate gene marker for selection and breeding decisions in genetic improvement of indigenous cattle for milk productivity.