Association between Mir-17-92 gene promoter polymorphisms and depression in a Chinese population.

BACKGROUND: Depression is a common chronic debilitating disease with a heavy social burden. single nucleotide polymorphisms (SNPs) can affect the function of microRNAs (miRNAs), which is in turn associated with neurological diseases. However, the association between SNPs located in the promoter region of miR-17-92 and the risk of depression remains unclear. Therefore, we investigated the association between rs982873, rs9588884 and rs1813389 polymorphisms in the promoter region of miR-17-92 and the incidence of depression in a Chinese population. METHODS: we used GWAS (Genome-wide association study) and NCBI (National Center for Biotechnology Information) to screen three SNPs in the miR-17-92 cluster binding sites. A case-control study (including 555 cases and 541 controls) was conducted to investigate the relationship between the SNPs and risk of depression in different regions of China. The gene sequencing ii was used to genotype the collected blood samples. RESULTS: the following genotypes were significantly associated with a reduced risk of depression: rs982873 TC (TC vs. TT: OR = 0.72, 95% CI, 0.54-0.96, P = 0.024; TC/CC vs. TT: OR = 0.74, 95% Cl, 0.56-0.96, P = 0.025); CG genotype of rs9588884 (CG vs. CC: OR = 0.74, 95% CI, 0.55-0.98, P = 0.033; CG/GG vs. CC: OR = 0.75, 95% Cl, 0.57-0.98, P = 0.036); and AG genotype of rs1813389 (AG vs. AA: OR = 0.75, 95% CI, 0.57-1.00, P = 0.049; AG/GG vs. AA: OR = 0.76, 95% Cl, 0.59-1.00, P = 0.047). Stratified analysis showed that there was no significant correlation between the three SNPS and variables such as family history of suicidal tendency (P > 0.05). CONCLUSIONS: our findings suggest that rs982873, rs9588884, and rs1813389 polymorphisms may be associated with protective factors for depression.

Association Between Single Nucleotide Polymorphisms Within lncRNA NONHSAT102891 and Depression Susceptibility in a Chinese Population.

Background: Depression is among the most common psychiatric disorders, and is a leading cause of the global disease burden. Its pathophysiological mechanism is unclear, which limits the development of therapeutic strategies. Long non-coding RNA (lncRNA) single nucleotide polymorphisms (SNPS) may be related. In this study, we aimed to determine the effects of the rs2242385, rs155979, rs3762983, and rs3762984 polymorphisms in the lncRNA NONHSAT102891 on depression susceptibility in a Chinese population. Methods: We conducted a case-control study in a cohort of 480 patients with depression and 329 healthy controls, and performed genotyping by gene sequencing ii. Results: The rs155979 GC genotype was significantly associated with increased risk of depression compared with healthy controls. Stratified analysis showed a 2.08-fold increased risk of suicide in patients with rs155979 GC or GG genotype. The rs2242385, rs3762983, and rs3762984 polymorphisms were not significantly associated with the risk of depression. Haploid analysis showed linkage disequilibrium between rs155979, rs3762983, and rs3762984, and the CCG haplotype reduced the risk of depression. Limitations: The study sample was relatively small, and was restricted to patients from central and southern China. Further, only peripheral blood was used for DNA extraction. Conclusion: The rs155979 polymorphism may be associated with the occurrence of depression in the Chinese population. However, further studies are needed to verify the reliability of our results in large populations and different ethnic groups.

Correlation between variants of the CREB1 and GRM7 genes and risk of depression.

The pathogenesis of depression involves cAMP-response element binding protein1 (CREB1) and metabotropic glutamate receptor 7 (GRM7), and their genetic polymorphisms may affect susceptibility to depression. The purpose of this study was to investigate whether the CREB1 polymorphisms rs2253206 and rs10932201 and the GRM7 polymorphism rs162209 are associated with the risk of depression. Using polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing, we analyzed the rs2253206, rs10932201, and rs162209 frequencies in 479 patients with depression and 329 normal controls. The results showed that the rs2253206 and rs10932201 polymorphisms were significantly associated with an increased risk of depression. However, no association was found between rs162209 and depression risk. When the data were stratified for several disease-related variables, none of the three polymorphisms were found to be correlated to onset, disease severity, family history, or suicidal tendency. Thus, the present findings indicate that the CREB1 polymorphisms rs2253206 and rs10932201 may be related to the occurrence of depression.

Haplotype analysis of long-chain non-coding RNA NONHSAT102891 promoter polymorphisms and depression in Chinese individuals: A case-control association study.

BACKGROUND: Our previous study reported that the single-nucleotide polymorphism (SNP) rs155979 GC in the promoter region of long-chain non-coding RNA (lncRNA) NONHSAT102891 affects depression susceptibility in a Chinese population. AIM: To explored associations of two SNPs and haplotypes in the lncRNA NONHSAT102891 promoter region with depression susceptibility in Chinese population. METHODS: This this case-control association study was approved by the Ethics Committee of Chengdu Medical College (approval number: 201815). Patient diagnosis was based on DSM-IV criteria. We selected a total of 480 patients with depression and 329 healthy controls with no history of psychopathology, and performed genotyping of two SNPs by extracting peripheral venous blood samples from the subjects. The function of the two lncRNA NONHSAT102891 promoter G/C and A/T haplotypes was detected by dual-luciferase reporter assays of human embryonic kidney 293T transfected cells. RESULTS: Stratified analysis of clinical and genotypic characteristics of our cohort showed that the degree of mild depressive episodes associated with the rs6230 TC/CC genotype increased by 1.59 times [TC/CC vs TT: odds ratio (OR) = 1.59, 95% confidence interval (CI): 1.08-2.35, P = 0.019]. The haploid analysis revealed linkage disequilibrium between rs3792747 and rs6230, and the double SNP CG haplotype was more common in the control group compared to case group, indicating that this haplotype significantly reduced the risk of depression (C/G vs T/A: OR = 0.42, 95%CI: 0.21-0.83, P = 0.01). There was no significant difference in the dual-luciferase reporter activity of the G/C and A/T haplotypes compared with the control group (P > 0.05), indicating that the double SNP haplotype has no transcriptional activity. CONCLUSION: The rs3792747 and rs6230 CG haplotypes of the lncRNA NONHSA T102891 promoter may be related to a reduced risk of depression in the Han Chinese population.

Association between Genetic Polymorphisms in Methylenetetrahydrofolate Reductase and Risk of Autoimmune Diseases: A Systematic Review and Meta-Analysis.

Methylenetetrahydrofolate reductase (MTHFR) is a critical rate-limiting enzyme in the homocysteine/methionine metabolism pathway that is implicated in the pathogenesis and progression of autoimmune diseases. Previous association studies have been performed to investigate the effect of polymorphisms in MTHFR on the risk of autoimmune diseases with inconsistent results. Therefore, this meta-analysis was designed to assess the association between the MTHFR 677 C/T and 1298 A/C polymorphisms and the susceptibility to autoimmune diseases. We identified reports by a literature search in the following electronic databases: PubMed, Ovid, Web of science, and China National Knowledge Infrastructure. Statistical analyses of the summary odds ratios (ORs) and 95% confidence intervals (CIs) were done using STATA software. In a recessive genetic model, the MTHFR 677 C/T polymorphism was associated with an increased risk of Behcet's disease (OR = 1.97, 95% CI, 1.31-2.97), multiple sclerosis (OR = 1.57, 95% CI, 1.03-2.38), and ankylosing spondylitis (OR = 2.90, 95% CI, 1.92-4.38). The MTHFR 1298 A/C polymorphism was associated an increased risk of multiple sclerosis in a heterozygote comparison (OR = 2.36, 95% CI, 1.29-4.30) and in a dominant model (OR = 2.31, 95% CI, 1.24-4.29). This meta-analysis demonstrated that the MTHFR 677 C/T was a risk factor for Behcet's disease, multiple sclerosis, and ankylosing spondylitis, and the 1298 A/C was a risk factor for multiple sclerosis.

The methylenetetrahydrofolate reductase 1298 A>C polymorphism is associated with an increased risk of inflammatory bowel disease: evidence from a meta-analysis.

OBJECTIVE: The association between genetic variants in methylenetetrahydrofolate reductase (MTHFR) and risk for inflammatory bowel disease (IBD) has been widely studied. However, the results are equivocal. In this meta-analysis, we aimed to determine the association between MTHFR polymorphisms and susceptibility to IBD. METHODS: We retrieved studies from the PubMed, Web of Science, Ovid, and China National Knowledge Infrastructure databases. Data were analyzed using STATA software; odds ratios (OR) and confidence intervals (CI) were calculated using fixed or random effects models. RESULTS: A marginally significant association of the MTHFR 677 C > T polymorphism and patients' IBD risk was observed in the overall analysis (OR = 1.11, 95% CI, 1.01-1.23), but not in the analysis of high-quality studies. However, for the MTHFR 1298 A > C polymorphism, a significant association was found between the MTHFR 1298 AC/CC genotypes and IBD risk in the overall analysis (OR = 1.26, 95% CI, 1.10-1.44), in the high-quality studies (OR = 1.20, 95% CI, 1.02-1.41), and in patients with ulcerative colitis (OR = 1.28, 95% CI, 1.10-1.48). CONCLUSIONS: Evidence from this meta-analysis indicates that the MTHFR 1298 A > C polymorphism may be responsible for susceptibility to IBD and ulcerative colitis.

N6-methyladenosine RNA modification: A promising regulator in central nervous system injury.

In addition to DNA methylation, reversible epigenetic modification occurring in RNA has been discovered recently. The most abundant type of RNA methylation is N6-methyladenosine (m6A) modification, which is dynamically regulated by methylases ("writers"), demethylases ("erasers") and m6A-binding proteins ("readers"). As an essential posttranscriptional regulator, m6A can control mRNA splicing, processing, stability, export and translation. Recent studies have revealed that m6A modification has the strongest tissue specificity for brain tissue and plays crucial roles in central nervous system (CNS) injures by affecting its downstream target genes or non-coding RNAs. This review focuses on the expression and function of m6A regulatory proteins in CNS trauma in vitro and in vivo. We also highlight the latest insights into the molecular mechanisms of pathological damage in the CNS. Understanding m6A dynamics, functions, and machinery will yield an opportunity for designing and developing novel therapeutic agents for CNS injuries.

A Meta-Analysis of 5-Hydroxytryptamine Receptor 1B Polymorphisms With Risk of Major Depressive Disorder and Suicidal Behavior.

Purpose: Previous association studies have investigated whether genetic polymorphisms in HTR1B influenced individuals' susceptibility to major depressive disorder (MDD), anti-depressant response (ADR) and suicidal behavior. However, equivocal evidence was obtained. In this meta-analysis, we aimed to examine the association of HTR1B polymorphisms with risk of MDD, ADR and suicidal behavior. Materials and Methods: Studies evaluating the association between HTR1B polymorphisms and risk of MDD, ADR and suicidal behavior were searched in Pubmed, Ovid Medline, web of science and China National Knowledge Infrastructure databases. Summary odds ratios (ORs), 95 % confidence intervals (CIs) and p-values were calculated using a fixed or random effects model. Results: Meta-analysis findings revealed a significantly increased risk of MDD with rs6296 GC and GC/CC genotypes (GC vs. GG: OR = 1.26, 95% CI, 1.07-1.48; GC/CC vs. GG: OR = 1.22, 95% CI, 1.04-1.43, respectively). Moreover, rs6298 CT genotype was significantly associated with an increased risk of suicidal behavior (CT vs. CC: OR = 1.48, 95% CI, 1.16-1.88). However, both rs6296 and rs130058 were not significant risk factors for lethal suicidal behavior. Conclusion: This meta-analysis identified that rs6296 and rs6298 in HTR1B may be significantly related to the risk of MDD and lethality of suicide attempts, respectively. Further studies are required to assess the markers in larger cohorts.

Relationship between mortality in people with mental disorders and suicide mortality in China during 2000 to 2014: An observational study.

Suicide is one of the top 10 causes of death in many countries. Although there are many studies on mental disorders, few studies have examined mortality in suicide population and mentally ill population. This study examined the association between mortality and mental disorders using data on suicides and mental disorders in China. Data from China's Health and Family Planning Statistical Yearbook for 2000 to 2014 were used to analyze the relationship between mortality associated with suicide and mental disorders. The analyses found that mortality among people with mental disorders dropped from 5.42/10 million in 2000 to 2.68/10 million in 2014, decreased more among females than males, and differed between urban and rural areas; that suicide mortality dropped from 10.79/10 million in 2000 to 6.79/10 million in 2014; the decrease was greater in women than in men, with suicide being highest among male residents of cities; and no significant correlation was found between mortality among persons with mental disorders and suicide mortality. There was no correlation between suicide mortality and mental-disorder mortality during 2000 to 2014; however, overall mortality decreased more among females than males during this period.

Pretreatment neutrophil-lymphocyte and platelet-lymphocyte ratio predict clinical outcome and prognosis for cervical Cancer.

Variations in systemic inflammatory response biomarker levels have been associated with adverse clinical outcome in various malignancies. In this study, we aimed to evaluate the predictive and prognostic role of the pretreatment neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in cervical cancer. We retrospectively investigated 616 patients who underwent initial radical hysterectomy with pelvic lymphadenectomy for cervical cancer between July 2012 and December 2014 in China. Their clinical and histopathological markers and complete blood counts were obtained and analyzed. Then we chose the group of 339 of the total 616 patients who were not combined preoperative radiotherapy or chemotherapy for the survival analysis. Prognostic factors were assessed by univariate and multivariate analyses. The ROC curve revealed NLR and PLR had significant ability to predict parametrial involvement, and the cutoff values for NLR and PLR were 2.5 and 138.8 respectively. Clinicopathologic analysis showed that NLR was linked to age, parametrial involvement, tumor-invasion depth and histologic grade, and PLR was related to age, parametrial involvement, tumor-invasion depth and FIGO stage. Univariate analysis identified high PLR as a significant poor predictor for progression-free survival (PFS) and overall survival (OS), and NLR exhibited no predict power on OS or PFS. Multivariable analysis showed that PLR was an independent predictor of PFS, but not OS. NLR and PLR were associated with the clinical characteristics of cervical cancer. Additionally, PLR had independence prognostic value for PFS in patients with cervical cancer receiving radical hysterectomy with pelvic lymphadenectomy.

Functional polymorphisms in the promoter region of miR-17-92 cluster are associated with a decreased risk of colorectal cancer.

miR-17-92 cluster is identified as a potential oncogenic miRNA. The aim of this study was to investigate the association of polymorphisms in the promoter region of miR-17-92 cluster with the risk of colorectal cancer (CRC). Three polymorphisms (i.e., rs9588884, rs982873 and rs1813389) in the promoter of miR-17-92 were analyzed among 874 cases and 1132 controls using a TaqMan allelic discrimination assay or a polymerase chain reaction-restriction fragment length polymorphism method. Relative expression of miR-17-92 was examined among CRC tumors and noncancerous tissues using quantitative reverse transcription-PCR. Transcriptional activities were measured using dual-luciferase reporter assay. We found a significantly reduced CRC risk with the rs9588884 (GG vs. CC: adjusted OR = 0.46, 95% CI, 0.35-0.62; dominant model: adjusted OR = 0.72, 95% CI, 0.59-0.86; recessive model: adjusted OR = 0.53, 95% CI, 0.40-0.69) and the rs982873 (CC vs. TT: adjusted OR = 0.60, 95%CI, 0.46-0.80; recessive model: adjusted OR = 0.62, 95% CI, 0.49-0.80). Haplotype analysis showed that the GCG haplotype had a decreased risk for CRC compared to the CTA haplotype (adjusted OR = 0.67, 95% CI, 0.57-0.79). The rs9588884 GG displayed a lower level of miR-20a and the rs982873 CC displayed a lower level of miR-17. Additionally, the rare allele of rs9588884 G and the rs982873 C revealed a reduced luciferase activity. These findings indicate that the rs9588884 GG and the rs982873 CC in the promoter of miR-17-92 may protect against CRC, possibly by decreasing transcriptional activity and eventually resulting in lower levels of miR-20a and miR-17.

A polymorphism rs4705341 in the flanking region of miR-143/145 predicts risk and prognosis of colorectal cancer.

The aim of this study was to investigate the effect of a polymorphism rs4705341 in the flanking region of miR-143/145 on the risk of colorectal cancer (CRC). The rs4705341 polymorphism was analyzed in 1002 cases and 1062 controls using a polymerase chain reaction-restriction fragment length polymorphism method. We found a significantly reduced CRC susceptibility with miR-143/145 rs4705341 in homozygote comparison (adjusted OR = 0.66, 95%CI, 0.50-0.88, P = 0.004), dominant genetic model (adjusted OR = 0.80, 95%CI, 0.67-0.96, P = 0.015), recessive genetic model (adjusted OR = 0.73, 95%CI, 0.56-0.94, P = 0.016), and allele comparison (adjusted OR = 0.83, 95%CI, 0.73-0.94, P = 0.004). Stratification analysis showed that the rs4705341 was related to differentiated status, clinical stage I-II, and patients without lymph node metastasis. Moreover, patients with rs4705341GG had a longer overall survival (adjusted HR = 5.57, 95%CI, 0.95-32.68). These findings indicate that the miR-143/145 rs4705341 may be used as a potential biomarker for the development and prognosis of CRC.

A functional variant rs353292 in the flanking region of miR-143/145 contributes to the risk of colorectal cancer.

MicroRNA (miR)-143 and miR-145 have been identified as molecular regulators in cell proliferation, cell growth, clone formation, apoptosis, cell cycle, invasion, and migration. We previously found that rs353292 in the flanking region of miR-143/145 showed a high frequency in patients with colorectal cancer (CRC). To identify whether the rs353292 polymorphism is a risk factor for CRC, we conducted this study with larger samples. A total of 809 patients with CRC and 1005 gender matched controls were collected. The rs353292 polymorphism was genotyped by using TaqMan allelic discrimination. Dual luciferase reporter assay was carried out to measure the transcriptional activity. We found that the rs353292 polymorphism was associated with an increased risk for developing CRC in heterozygous comparison (adjusted OR = 1.70, 95% CI, 1.32-2.20, P < 0.001), dominant genetic model (adjusted OR = 1.62, 95% CI, 1.26-2.09, P < 0.001), and allele comparison (adjusted OR = 1.46, 95% CI, 1.16-1.84, P = 0.001). The rs353292 CT/TT carriers exhibited a lower expression of miR-143 compared to the CC carriers (P = 0.04). Moreover, the pGL3-rs353292T displayed a significantly lower luciferase activity than pGL3-rs353292C (P < 0.01). These findings indicate that the rs353292 polymorphism is functional and may be a risk factor for the development of CRC.

Association between polymorphisms in long non-coding RNA PRNCR1 in 8q24 and risk of gastric cancer.

A long ncRNA (lncRNA) prostate cancer non-coding RNA 1 (PRNCR1) in the 8q24 has been reported to be upregulated in prostate cancer with a function of activating androgen receptor (AR). AR plays a key role in the gender disparity, cell migration, and invasion of gastric cancer (GC). We hypothesized that single nucleotide polymorphisms (SNPs) in the lncRNA PRNCR1 may be related to the risk of GC. We conducted a case-control study to investigate the association between SNPs in the lncRNA PRNCR1 and the risk of GC. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was used to determine the genotypes of 613 subjects including 219 cases with GC and 394 controls. We found that patients with the rs13252298AG genotype displayed a 1.50-fold increased risk of GC (AG vs. AA, 95 % confidence interval (CI) = 1.05-2.12, p = 0.02). Interestingly, the rs7007694CT and CC and the rs1456315GG genotypes displayed a decreased risk of GC (rs7007694CT vs. TT, odds ratio (OR) = 0.68, 95 % CI = 0.48-0.97, p = 0.03; rs7007694CC vs. TT, OR = 0.36, 95 % CI = 0.13-0.97, p = 0.04; rs1456315GG vs. AA, OR = 0.30, 95 % CI = 0.13-0.70, p = 0.004, respectively). Our results suggest that SNPs in the lncRNA PRNCR1 may be a biomarker for the etiology of GC.

Combined analysis of pri-miR-34b/c rs4938723 and TP53 Arg72Pro with cervical cancer risk.

miR-34 family members can form a p53-miR-34 positive feedback loop and induce apoptosis, DNA repair, angiogenesis, and cell cycle arrest. We conducted a case-control study to examine whether two polymorphisms (i.e., rs4938723 in the promoter of pri-miR-34b/c and TP53 Arg72Pro) were linked to the carcinogenesis of cervical cancer among Chinese Han women. Genotypes of the two polymorphisms in 328 cervical cancer patients and 568 control subjects were determined by using a polymerase chain reaction-restriction fragment length polymorphism assay. We found a significantly increased cervical cancer risk in the pri-miR-34b/c rs4938723 under dominant and overdominant model (CT/CC vs. TT: adjusted OR = 1.34, 95 % CI = 1.01-1.77; CT vs. TT/CC: adjusted OR = 1.37, 95 % CI = 1.05-1.80, respectively). Increased cervical cancer risks were also found in the TP53 Arg72Pro under a heterozygous comparison and overdominant model (CG vs. GG: adjusted OR = 1.44, 95 % CI = 1.06-1.95; CG vs. GG/CC: adjusted OR = 1.47, 95 % CI = 1.12-1.94, respectively). Stratification analysis showed that patients carrying the pri-miR-34b/c rs4938723 CT genotype had a significantly increased risk for developing poorly differential status and clinical stage I. Moreover, increased cancer risks were observed for the TP53 Arg72Pro polymorphism in patients with poorly differential status, clinical stage II, and without lymph node metastasis. Combined analysis revealed that the genotypes of rs4938723 CT/CC and TP53 Arg72Pro CG/CC had an increased cervical cancer risk (OR = 2.21, 95 % CI = 1.38-3.53). These findings suggest that the pri-miR-34b/c rs4938723 and TP53 Arg72Pro polymorphisms may contribute to the genesis of cervical cancer.

Pri-Mir-34b/C and Tp-53 Polymorphisms are Associated With The Susceptibility of Papillary Thyroid Carcinoma: A Case-Control Study.

Tumor suppressor p53 directly regulated the abundance of the miR-34b/c. The interaction might contribute to certain cancer. We hypothesized that rs4938723 in the promoter region of pri-miR-34b/c and TP-53 Arg72Pro may be related to the risk of papillary thyroid carcinoma (PTC). A total of 784 patients with PTC and 1006 healthy controls were recruited to participate in this study. The variants were discriminated using a polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP). Additionally, the relative expression levels of miR-34b/c and TP-53 in 44 paired samples were revealed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). A significantly increased risk of PTC was observed in the miR-34b/c rs4938723 CT, CC, and CT/CC genotypes compared with the TT genotype (CT vs TT: adjusted odds ratio [OR] = 1.51, 95%confidence interval [CI] = 1.23-1.85; CC vs TT: adjusted OR = 1.89, 95%CI = 1.39-2.63; CT/CC vs TT: adjusted OR = 1.59, 95%CI = 1.30-1.92, respectively). Significantly increased PTC susceptibility was also associated with the TP-53 Arg72Pro CC and CG/CC genotypes compared with the GG genotype (CC vs GG: adjusted OR = 2.04, 95%CI = 1.54-2.70; CG/CC vs GG: adjusted OR = 1.35, 95%CI = 1.11-1.67, respectively). Stratification analysis revealed that patients carrying the TP-53 Arg72Pro C allele and CC genotype had a significantly increased risk for developing N1 (C vs. G: OR = 1.27, 95%CI = 1.03-1.56; CC vs. GG: OR = 1.62, 95%CI = 1.07-2.46, respectively). Combined analysis showed that the genotypes of rs4938723 CT/CC + TP-53CG/CC increased the risk of PTC compared with rs4938723TT + TP-53GG (OR = 2.25, 95%CI = 1.67-3.03). Additionally, level of miR-34b was significantly upregulated in PTC patients.These findings indicate that the miR-34b/c rs4938723 and TP-53 Arg72Pro polymorphisms may contribute to the susceptibility of PTC.

A Functional Polymorphism in the Promoter of MiR-143/145 Is Associated With the Risk of Cervical Squamous Cell Carcinoma in Chinese Women: A Case-Control Study.

MiR-143/145 is down-regulated in cervical cancer, which may serve as a tumor suppressor by targeting KRAS and Ras-responsive element-binding protein (RREB1). Activated KRAS leads to down-regulation of miR-143/145 transcription in a RREB1-dependent manner, establishing a miR-143/145-KRAS-RREB1 feedback loop. A polymorphism rs4705343C/T in the promoter of miR-143/145 might influence the binding of TATA-binding protein. We hypothesized that the miR-143/145 rs4705343 and KRAS rs712 may be related to the occurrence of cervical squamous cell carcinoma (CSCC). In this study, we genotyped the 2 polymorphisms in 415 patients with CSCC and 504 controls using polymerase chain reaction-restriction fragment length polymorphism. The promoter activities were measured by the Dual-Luciferase Reporter Assay System. We found that the rs4705343TC genotype was associated with an increased risk of CSCC (adjusted odds ratio [OR] = 1.37; 95% confidence interval [CI], 1.05-1.80). The significantly increased association was also observed in a dominant genetic model (adjusted OR = 1.32; 95% CI, 1.01-1.72). Combined analysis showed that individuals carrying the genotypes of rs4705343 TC/CC and rs712GT/TT had a 1.47-fold increased risk of CSCC (adjusted OR = 1.47; 95% CI, 1.01-2.15). By using multifactor dimensionality reduction software method, we identified a significant interaction between the miR-143/145 rs4705343 and KRAS rs712. Dual-Luciferase Reporter Assay showed that the luciferase activity was significantly lower in cells transfected with the rs4705343C allele than that of the rs4705343T allele. These findings indicate that miR-143/145 rs4705343 and KRAS rs712 may contribute to the etiology of CSCC in Chinese women.

Interaction analysis of IL-12A and IL-12B polymorphisms with the risk of colorectal cancer.

IL-12 is an antitumor cytokine with functions of inhibiting tumor growth, invasion, and metastasis, indicating that IL-12 is a promising candidate for cancer treatment. The aim of this study was to investigate the association of IL-12A rs568408, IL-12A rs2243115, and IL-12B rs3212227 with the susceptibility to colorectal cancer (CRC). Two hundred and fifty-seven histopathologically confirmed CRC patients and 236 age- and gender-matched controls were enrolled. The three polymorphisms were genotyped using a polymerase chain reaction-restriction fragment length polymorphism assay. We found that the IL-12A rs568408 AG/AA genotypes were associated with an increased risk of CRC with an adjusted odds ratio (OR) of 1.66 (95 % confidence interval (CI), 1.11-2.48). Stratified analyses showed that patients carrying the IL-12B rs3212227AC/CC genotypes had a 1.97-fold increased risk of tumor metastasis (OR = 1.97; 95 % CI, 1.04-3.70). Gene-gene interaction analysis showed that subjects carrying the IL-12A rs568408AG/AA and IL-12B rs3212227AA genotypes had a 2.40-fold increased risk of CRC (OR = 2.40; 95 % CI, 1.14-5.07) and individuals carrying the IL-12A rs568408AG/AA and IL-12B rs3212227AC/CC genotypes had a 1.93-fold increased risk of CRC (OR = 1.93; 95 % CI, 1.10-3.41). These findings indicate that IL-12A rs568408 and IL-12B rs3212227 may be related to the development of CRC.

Genetic variants in the promoters of let-7 family are associated with an increased risk of major depressive disorder.

BACKGROUND: Let-7 family plays a critical role in the pathogenesis of major depressive disorder (MDD). Genetic polymorphisms in the promoters of miRNA may influence individual׳s susceptibility to diseases. The purpose of this study was to investigate the association between rs10877887 and rs13293512 polymorphisms in the promoters of let-7 family and the risk of MDD. METHOD: Polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing assays were used to analyze the rs10877887 and rs13293512 polymorphisms in 237 MDD patients and 296 controls. RESULTS: We found that the rs10877887 CC genotype was associated with an increased risk of MDD (CC vs. TT: OR=1.73, 95% CI, 1.04-2.86, P=0.03, and CC vs. TT/TC: OR=1.74, 95% CI, 1.08-2.80, P=0.02, respectively). Similarly increased risk was also observed for the rs13293512 (CC vs. TT: OR=1.83, 95% CI, 1.12-2.99, P=0.015; CC vs. TT/TC: OR=1.84, 95% CI, 1.20-2.81, P=0.005; and C vs. T: OR=1.32, 95% CI, 1.03-1.68, P=0.03, respectively). Stratification analysis showed that patients with the rs13293512 TC and CC genotypes had a 2.29 and 2.56-fold increased risk of MDD recurrence after treatment (TC vs. TT: 95% CI, 1.23-4.25, P=0.008; CC vs. TT: 95% CI, 1.25-5.23, P=0.009, respectively). LIMITATIONS: Relatively small sample size and hospital-based study design may influence the results. CONCLUSIONS: Our findings suggest that the rs10877887 and rs13293512 polymorphisms may be related to the development of MDD.

A functional insertion/deletion polymorphism in the promoter region of the NFKB1 gene increases the risk of papillary thyroid carcinoma.

This study aimed to assess whether an insertion/deletion polymorphic variation rs28362491 in the NFKB1 promoter region was related to the risk of papillary thyroid carcinoma (PTC). Genomic DNA was extracted from the peripheral venous blood of 352 patients with PTC and 459 controls. The NFKB1 rs28362491 polymorphism was genotyped by using a polymerase chain reaction assay. We found that the frequency of the heterozygous genotype ATTG1/ATTG2 was significantly higher in the cases compared to the controls (odds ratios [OR]=1.44, 95% confidence intervals [CI]=1.05-1.96, p=0.02). Moreover, the frequency of ATTG1/ATTG2+ATTG1/ATTG1 genotypes was significantly elevated in the cases compared to the controls (OR=1.38, 95% CI=1.03-1.85, p=0.03). These findings suggest that the -94 insertion/deletion ATTG polymorphism in the NFKB1 promoter might be associated with an increased risk of PTC.