Allelic Genetic Models Research Articles

Genetic association of hypoxia inducible factor 1-alpha (HIF1A) Pro582Ser polymorphism with risk of diabetes and diabetic complications.

Diabetes is an age-related chronic disease associated with a number of complications, emerging as one of the major causes of morbidity and mortality worldwide. Several studies indicated that hypoxia-inducible factor 1-alpha (HIF1A) genetic polymorphisms may be associated with diabetes and diabetic complications. However, this association remains ambiguous. Thus, we performed a meta-analysis to provide more precise conclusion on this issue. Odds ratios (OR) with corresponding 95% confidence intervals (CI) were applied to assess the strength of the relationships. There was a protective association between HIF1A Pro582Ser polymorphism and diabetes under the heterozygous genetic model (OR = 0.70, 95% CI = 0.55-0.91; P = 0.007). Similar associations were observed in diabetic complications risk under the allelic (OR = 0.69, 95% CI = 0.57-0.83; P < 0.001), homozygous (OR = 0.51, 95% CI = 0.30-0.87; P = 0.014), recessive (OR = 0.73, 95% CI = 0.59-0.90; P = 0.004) and dominant (OR = 0.40, 95% CI = 0.25-0.65; P < 0.001) genetic models. No effects of the HIF1A Ala588Thr polymorphism were found in risk of diabetes and diabetic complications. Taken together, these findings revealed the protective effect of HIF1A Pro582Ser polymorphism against diabetes and diabetic complications.

Lack of Evidence for an Association between IL-17F Rs763780 Polymorphism and Pulmonary Tuberculosis

ABSTRACT The relationship between the interleukin-17F (IL-17F) rs763780 polymorphism and tuberculosis (TB) has been a source of debate. The potential association between the IL-17F rs763780 polymorphism and TB was investigated using a meta-analysis of case-control studies, which were obtained using the EMBASE, PubMed, CNKI, Scopus, and Web of Science databases. Heterogeneity across studies was evaluated, and summary odds ratios and 95% confidence intervals were computed to estimate a summary effect size using either a fixed-effects or random-effects model. Eight eligible studies comprising nine comparisons for the IL-17F rs763780 polymorphism (3824 cases and 3787 controls) were obtained for this meta-analysis. Although a significant relationship between IL-17F rs763780 and TB susceptibility was observed using the allele genetic model (odds ratio = 1.34, 95% confidence interval = 1.04–1.74), there was high heterogeneity among the studies (I2 = 79%, P=0.0001). The stratified analyses by race, type of tuberculosis, and Hardy–Weinberg equilibrium suggested that the IL-17F rs763780 polymorphism was not associated with risk of pulmonary tuberculosis and the heterogeneity disappeared. Hardy–Weinberg equilibrium is the main cause of the heterogeneity. No evidence was found through this meta-analysis that suggested an association between the IL-17F rs763780 polymorphism and risk of pulmonary tuberculosis.

Association between miRNA-146a polymorphism and lung cancer susceptibility: A meta-analysis involving 6506 cases and 6576 controls.

We sought to analyze the association between miR-146a rs2910164 G > C polymorphism and susceptibility to lung cancer using a meta-analysis of case-control studies. We systematically searched for studies reporting on the relationship between miR-146a rs2910164 polymorphism and the risk of lung cancer in PubMed, Embase, Web of Science and Chinese National Knowledge Infrastructure databases. We then calculated pooled odds ratios (ORs), at 95% confidence interval (CI) to assess the aforementioned relationship. All the data were analyzed using statistical packages implemented in R version 3.6.2 (R Project for Statistical Computing), run in RStudio version 1.2.5033. A total of fifteen studies, comprising 6506 cases and 6576 controls, were enrolled in this meta-analysis. Significant associations were observed between miR-146a rs2910164 polymorphism and the risk of lung cancer based on overall pooled subjects under the allele, heterozygous, homozygous, dominant, and recessive genetic models (C vs. G: OR = 1.27, 95% CI: 1.12-1.44; GC vs. GG: OR = 1.23, 95% CI: 1.03-1.46; CC vs. GG: OR = 1.51, 95% CI: 1.18-1.93; GC + CC vs. GG: OR = 1.33, 95% CI: 1.10-1.61; CC vs. GG + GC: OR = 1.32, 95% CI: 1.13-1.53). Ethnicity-based subgroup analyses revealed no statistically significant differences in Asians using heterozygous and dominant genetic models. miR-146a rs2910164 G > C polymorphism may be a risk factor of lung cancer. Asian populations exhibiting heterozygous and dominant genotypes need to be further investigated to validate our findings.

Genetic variations associated with telomere length affect the risk of gastric carcinoma.

This study aimed to further understand the role of relative telomere length (RTL) in susceptibility to gastric carcinoma (GC) and investigate the association between genetic polymorphisms in the telomere length related genes and GC risk.RTL was measured using the real-time quantitative polymerase chain reaction from 1000 patients and 1100 healthy controls. Genotyping was performed using the Agena MassARRAY platform. The statistical analysis was performed using the chi-square/ Welch T tests, Mann-Whitney U test, and logistic regression analysis.The association analysis of telomere length and GC showed that the RTL in the case group was shorter than in the controls, and the shorter RTL was associated with an increased risk of GC. The association analysis between telomere length related genes polymorphisms and genetic susceptibility to GC indicated that: In the allele models and genetic models, TERT (rs10069690, rs2242652 and rs2853676) and TN1F1 (rs7708392 and rs10036748) were significantly associated with an increased risk of GC. In addition, the haplotype 'Grs10069690Crs2242652" of TERT and the haplotype 'Grs7708392Trs10036748" of TNIP1 were associated with an increased risk of GCOur results suggested that shorter RTL was associated with an increased risk of GC; The association analysis have identified that the TERT (rs10069690, rs2242652 and rs2853676) and TN1P1 (rs7708392 and rs10036748) were associated with GC risk.

The Association Between Interleukin-6 Promoter Polymorphisms and Rheumatoid Arthritis by Ethnicity: A Meta-Analysis of 33 Studies.

We performed a meta-analysis to determine the effect Interleukin-6 (IL-6) promoter polymorphism (-174 G>C, -572 G>C, and -597 G>A) have on the development rheumatoid arthritis (RA) by ethnicity. PubMed, EBSCO, LILACS, and Scopus databases were searched for studies exploring the association between any IL6 polymorphisms and RA until November 2018. Genotype distributions were extracted and, depending on the level heterogeneity, determined by the ψ2-based Q test and the Inconsistency Index (I2), fixed-effects or random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models. From 708 identified publications, 33 were used in this analysis. For the -174 polymorphism, Asians (ORheterozygous=7.57, 95%CI: 2.28-25.14, ORhomozygous=5.84, 95%CI: 2.06-16.56, ORdominant=7.21, 95%CI: 2.30-22.63, ORrecessive=5.04, 95%CI: 1.78-14.28, ORallelic=6.60, 95%CI: 2.26-19.28, p<.05) and Middle East countries (ORheterozygous=2.30, 95%CI: 1.10-4.81, ORdominant=2.27, 95%CI: 1.22-4.22, ORallelic=2.29, 95%CI: 1.24-4.23, p<.05) were associated with a significant risk of developing RA. Whereas, for Latinos, the C-allele was associated with a benefit (ORhomozygous=0.26, 95%CI: .08-.82, ORrecessive=.25, 95%CI: .08-.80, p<.05). For the -572 polymorphism, Asians demonstrated a significant association for the homozygous and recessive genetic models (8 studies, ORhomozygous=1.56, 95%CI: 1.16-2.09, ORrecessive=1.63, 95%CI: 1.08-2.45, p<.05). For the -597 polymorphism, no association was observed. Here, the -174 G>C polymorphism increased the risk of developing RA in Asians and Middle East populations. Interestingly, for Latinos, the polymorphism was associated with a benefit. For the -572 polymorphism, only the Asian population showed an increased risk of developing RA for the CC genotype.

Genetic association between HOTAIR gene and the risk of cancer: an updated meta-analysis

Several recent investigations show that HOX transcript antisense intergenic RNA (HOTAIR) play an important role in the pathogenesis of different cancers. HOTAIR polymorphisms has been widely studied in the context of association between with the risk of cancer pathogenesis. However, there is no certain conclusion about the role of HOTAIR polymorphisms in different cancer initiation and progression. Our team has selected eligible studies up to 1 May 2019, from several electronic databases, including Web of Science, PubMed, Scopus, and Google Scholar databases. We have included total number of 102 case-control investigations extracted from 41 eligible articles for the current meta-analysis. We calculated pooled odds ratio (ORs) with their corresponding 95% confidence intervals (CIs) using either fixed-effect or random-effect models for quantitative evaluation of the strength for the association between HOTAIR gene polymorphisms and the risk of cancer. Our current meta-analysis investigation showed that HOTAIR rs4759314 polymorphism particularly increased the overall risk of cancer in different models including homozygous, recessive and allele genetic. HOTAIR rs920778 significantly raised the cancer risk only in recessive genetic model. HOTAIR rs12826786 polymorphism was associated with cancer development in heterozygous, homozygous, dominant, recessive and allele genetic models. Also, an increase in cancer risk was observed with rs874945 polymorphism of HOTAIR gene in heterozygous, dominant and allele genetic models. The rs12427129 polymorphism showed correlation with cancer susceptibility only in recessive model. Subgroup analysis based on cancer type suggested that rs4759314 polymorphism significantly increased the risk of gastric and cervical cancers, and the rs920778 polymorphism increased the risk of gastrointestinal, cervical and gastric cancers. In summary, this study found that HOTAIR polymorphisms are significantly associated with cancer development.

Association of rs610604 in TNFAIP3 and rs17728338 in TNIP1 gene polymorphisms with psoriasis susceptibility: a meta-analysis of case-control studies

BackgroundTo date, the fundamental pathophysiology underlying the occurrence and progression of psoriasis are still unanswered questions. Genome-wide association surveys have revealed that TNFAIP3 and TNIP1 were key biomarkers for psoriasis. Here, we intended to conduct a survey on the association between TNFAIP3 and TNIP1 gene polymorphisms and psoriasis risk.MethodsA comprehensive search of four online databases—China National Knowledge Infrastructure (CNKI), PubMed, Embase, and Cochrane Library was undertaken up to August 25, 2019. We chose allele genetic model to deal with the original data. Newcastle–Ottawa scale (NOS) was used to evaluate the risk bias of each study. The RevMan 5.3 software was used to calculate the combined odds ratio and 95% confidence interval.ResultsIn total, we included 13 case-control studies consist of 13,908 psoriasis patients and 20,051 controls in this work. Our results demonstrated that rs610604 in TNFAIP3 polymorphism was significantly associated with psoriasis risk using random-effect model (G vs. T, OR = 1.19, 95% CI: 1.09–1.31, P = 0.0002), and a significant association between rs17728338 in TNIP1 polymorphism and psoriasis vulnerability using fixed-effect model (A vs. G, OR = 1.69, 95% CI:1.58–1.80, P < 0.00001).ConclusionsOur findings indicated that rs610604 in TNFAIP3 and rs17728338 in TNIP1 gene polymorphisms were associated with psoriasis susceptibility.

Association between PPARγrs1801282 polymorphism with diabetic nephropathy and type-2 diabetes mellitus susceptibility in south India and a meta-analysis

BackgroundDiabetic Nephropathy (DN) is a major complication of Type 2 Diabetes Mellitus (T2DM) with high morbidity rates worldwide. ObjectiveTo determine the association of PPARγ rs1801282 polymorphism in T2DM and DN in south Indian population. MethodsWe have conducted a case–control study to test the association of rs1801282 polymorphism with T2DM and DN in 424 subjects (DN=128; T2DM=148 and controls=148) belonging to the south Indian population using ARMS-PCR and Sanger sequencing method. Further, a meta-analysis was performed for rs1801282 polymorphism from the published literature retrieved from various electronic databases to determine the susceptibility among T2DM and DN across various ethnic populations under five genetic models. ResultsThe genotyping of rs1801282 polymorphism showed significant (p-value<0.05) association with DN and T2DM compared to controls. In the meta-analysis, no significant association (p-value>0.05) was noticed for rs1801282 with DN vs. controls in homozygote, heterozygote, allelic, recessive and dominant genetic models. However, a significant association was observed between rs1801282 SNP and T2DM under heterozygote (Jj vs JJ) genetic model with OR=0.56, (95%CI [0.43–0.74]), p≤0.0001 of Asian and Caucasian populations. ConclusionOverall analysis suggests that the rs1801282 polymorphism might be associated with DN and T2DM. More case–control studies on the PPARγ gene with a larger sample size including all the confounding factors are required to corroborate the findings from this meta-analysis.

Association of EGLN2 rs10680577 Polymorphism with the Risk and Clinicopathological Features of Patients with Prostate Cancer

Several studies have evaluated the association between EGLN2 4-bp insertion/deletion (ins/del) polymorphism (rs10680577) and many cancers. However, up to date, no study has inspected the impact of rs10680577 polymorphism on prostate cancer (PCa) risk. This case-control study was achieved on 170 pathologically confirmed PCa patients and 196 cancer free men to inspect whether rs10680577 variant is related to the risk and clinicopathological features of patients with PCa. Genotyping was performed by mismatched polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The findings did not support an association between the variant with the risk and clinicopathological characteristics of PCa patients. When we pooled our results with six preceding studies, the findings suggested that rs10680577 variant significantly augmented the risk of overall cancer in heterozygous (OR=1.38, 95 % CI=1.26-1.52, p<0.00001, ins/del vs ins/ins), homozygous (OR=1.66, 95 % CI=1.05-2.61, p=0.029, del/del vs ins/ins), codominant (OR=1.44, 95%CI=1.32-1.58, p<0.00001, ins/del+del/del vs ins/ins), and allele (OR=1.32, 95%CI=1.18-1.49, p<0.00001, del vs ins) genetic models. Additional well designed studies with larger sample sizes are necessary to confirm our findings.

Association between PPARγrs1801282 polymorphism with diabetic nephropathy and type-2 diabetes mellitus susceptibility in south India and a meta-analysis

BackgroundDiabetic Nephropathy (DN) is a major complication of Type 2 Diabetes Mellitus (T2DM) with high morbidity rates worldwide. ObjectiveTo determine the association of PPARγ rs1801282 polymorphism in T2DM and DN in south Indian population. MethodsWe have conducted a case–control study to test the association of rs1801282 polymorphism with T2DM and DN in 424 subjects (DN=128; T2DM=148 and controls=148) belonging to the south Indian population using ARMS-PCR and Sanger sequencing method. Further, a meta-analysis was performed for rs1801282 polymorphism from the published literature retrieved from various electronic databases to determine the susceptibility among T2DM and DN across various ethnic populations under five genetic models. ResultsThe genotyping of rs1801282 polymorphism showed significant (p-value<0.05) association with DN and T2DM compared to controls. In the meta-analysis, no significant association (p-value>0.05) was noticed for rs1801282 with DN vs. controls in homozygote, heterozygote, allelic, recessive and dominant genetic models. However, a significant association was observed between rs1801282 SNP and T2DM under heterozygote (Jj vs JJ) genetic model with OR=0.56, (95%CI [0.43–0.74]), p≤0.0001 of Asian and Caucasian populations. ConclusionOverall analysis suggests that the rs1801282 polymorphism might be associated with DN and T2DM. More case–control studies on the PPARγ gene with a larger sample size including all the confounding factors are required to corroborate the findings from this meta-analysis.

Alcohol, Carbohydrate, and Calcium Intakes and Smoking Interactions with APOA5 rs662799 and rs2266788 were Associated with Elevated Plasma Triglyceride Concentrations in a Cross-Sectional Study of Korean Adults

BackgroundPlasma triglyceride (TG) concentrations are markedly higher among Asians, which may be associated with the interaction of genetics and lifestyle factors. ObjectiveThe purpose of this study was to investigate the genetic variants that have a strong association with plasma TG concentrations from genome-wide association study and to identify lifestyle interactions with the genetic variants that are associated with dyslipidemia in a cohort of Korean adults. DesignKorean genome and epidemiology study utilized a cross-sectional design of Koreans to determine genetic variants and lifestyle factors, including nutrient intakes, in a retrospective hospital-based city cohort conducted by the Korean Center for Disease and Control during 2004-2013. ParticipantsKorean adults aged 40 to 77 years were participants (n=28,445). Main outcome measuresThe genetic variants that influence plasma TG concentrations were selected by genome-wide association study using an allele genetic model after adjusting for age, sex, area of residence, and body mass index. Lipid profiles and nutrient intakes from food frequency questionnaires were measured. The interactions between the single nucleotide polymorphisms and lifestyle factors were determined to influence plasma TG levels. ResultsCarrying the minor alleles of APOA5 rs662799 and rs2266788 had an association with higher plasma TG concentrations by 1.86- and 1.51-fold, respectively, compared with those with the major allele (P=8.89E-150 and P=4.75E-68, respectively). Sex had an interaction with these single nucleotide polymorphisms, with males having higher plasma TG concentrations. The single nucleotide polymorphisms had significant interactions with carbohydrate, fat, and calcium intakes; alcohol consumption; and smoking status that were associated with plasma TG concentrations. Carriers with the minor allele of each single nucleotide polymorphisms had higher plasma TG concentrations when consuming-low fat (<15%) and high carbohydrate (≥72%) diets than those with major alleles. Carriers of the minor alleles with low calcium intakes (<500 mg/day) experienced elevated plasma TG concentrations compared with carriers of the major alleles. Smokers and alcohol drinkers with either of the minor alleles of APOA5, rs662799 or rs2266788, had higher plasma TG concentrations than those with its major allele. ConclusionsThese results indicated that carrying the minor alleles of APOA5 rs662799 and rs2266788, especially for men, was associated with elevated TG concentrations and suggested that Korean carriers of the minor alleles could be at increased risk of hypertriglyceridemia. Further research is needed to investigate the efficacy of modulating lifestyle factors to prevent dyslipidemia in people carrying the minor alleles of APOA5 rs662799 and rs2266788.

Association of TP53 rs1042522 with cervical cancer in the sub-Saharan African population: a meta-analysis.

TP53 plays a crucial role in preventing cancer development. Previous studies in sub-Saharan Africa (SSA) reported inconclusive findings for the association of the TP53 rs1042522 C>G variant with cervical cancer. We therefore performed a meta-analysis to summarise this association in the SSA population. Online databases were searched to identify suitable articles according to the PRISMA guidelines. We included studies published in English or French that provided the sample sizes and genotype counts for both cases and controls and evaluated the association between TP53 rs1042522 and cervical cancer in the SSA population. A fixed-effect model was used to calculate the pooled odds ratio (OR) and 95% confidence intervals (95% CIs). A total of 699 cervical cancer cases and 1008 controls from eight studies in SSA were included in this meta-analysis. Women harbouring the variant G allele of the TP53 rs1042522 were at increased risk of cervical cancer in allelic (G vs. C; OR=1.30, 95% Cl=1.12-1.50), homozygous (GG vs. CC; OR=1.62, 95% CI=1.20-2.19) and recessive (GG vs. CG+GG; OR=1.74, 95% CI=1.34-2.25) genetic models. However, the dominant genetic model (CG+GG vs. CC; OR=1.20, 95% CI=0.96-1.48) was not significantly associated with cervical cancer. Our meta-analysis revealed that harbouring variant G allele of TP53 rs1042522 is associated with cervical cancer risk in the SSA population.

Absence of significant association between UGT2B4 genetic variants and the susceptibility to anti-tuberculosis drug-induced liver injury in a Western Chinese population.

Combination regimens of six-month duration may increase the incidence of anti-tuberculosis drug-induced liver injury (ATLI), which is clinically characterized by mild cholestasis and hepatocanalicular lesions. UGT2B4 is a predominant UDP-glucuronosyltransferase enzyme in the human liver that plays an important role in the detoxification of bile acids, which yields water-soluble inactive compounds that can easily be excreted in the bile or urine. This study aimed to investigate the potential association between UGT2B4 variants and the susceptibility to ATLI. Genomic DNA was extracted from whole blood sample of each patient, and all SNPs were genotyped using an improved multiplex ligation detection reaction method. Clinical symptoms and laboratory results were recorded regularly. Five genetic variants at UGT2B4(rs1131878, rs1966151, rs28361541, rs4557343 and rs79407331) were identified in a prospective study of 118 ATLI cases and 628 non-ATLI controls. All participants were treated by first-line anti-TB drugs in Western China Hospital. The potential association between SNPs, ATLI risk and clinical phenotypes were determined based on the distribution of allelic frequencies and different genetic models. Statistical comparisons of cases and controls after correction for multiple testing did not yield any significant association between genetic variants at UGT2B4 and risk of ATLI via the analyses of single locus and subgroup differences. This is the first study aimed to investigate the association of UGT2B4 polymorphisms with ATLI risk. Our results revealed that UGT2B4 genetic variants are unlikely to confer susceptibility to ATLI in the Western Chinese Han population.

Association of cytokine Th2 gene polymorphisms with autoimmune thyroid diseases in Tunisian population.

Autoimmune thyroid diseases (AITD) including Graves' disease (GD) and Hashimoto's thyroiditis (HT) are complex genetic diseases. Th2 cytokines act on the development of AITD. This study was conducted on Tunisian patients with AITD to investigate the association of Th2 cytokine gene polymorphisms and haplotype combination with GD or HT risk. A total of 156 controls, 160 patients with HT and 88 patients with GD were genotyped for IL-4 rs2243250, IL-5 rs2069812, IL-6 rs1800796 and IL-13 rs1800925 polymorphisms by PCR-RFLP. The AITD risk was assessed by a logistic regression analysis using the SNP stats statistical program. False-positive report probability (FPRP) was estimated to evaluate significant findings. IL-13 rs1800925 was associated with GD, after adjustment for age and gender, in codominant, dominant and allele genetic models (p=.0072; p=.0018; p=.012, respectively). Significant association of the IL-6 rs1800796C/G genotype with GD was also detected (p=.025). Furthermore, increased risk of HT was still found for IL-13 rs1800925T allele (p=.039, OR=1.39) and for IL-4 rs2243250T/T genotype both in codominant (p=.033, OR=2.59) and recessive (p=.011, OR=2.73) models after adjustment for age and gender. Interestingly, haplotype analysis performed on the IL-4, IL-5 and IL-13 genes revealed a high risk of HT with CTT haplotype (p=.008, OR=2.12). However, the CCT haplotype is a protective factor (OR=0.36). Patients carrying the CT haplotype with only one minor allele had a moderate risk of HT (OR=1.56). The FPRP analysis showed that the association of IL-13 rs1800925 polymorphism with GD and HT and the association of CTT haplotype with HT were noteworthy. In conclusion, the IL-4, IL-5, IL-6 and IL-13 polymorphism may play a role in susceptibility to GD and HT in the Tunisian population. Furthermore, gene-gene interaction between the IL-4, IL-5 and IL-13 significantly increases the risk of AITD. Further studies with larger numbers of individuals are needed to confirm the results.

Vitamin D receptor rs2228570 polymorphism and Parkinson’s disease risk in a Chinese population

Epidemiological evidence of the relationship between vitamin D receptor (VDR) rs2228570 (FokI) polymorphism and the susceptibility of Parkinson’s disease (PD) is inconsistent, partially due to between-study variations in sample size, age, male/female ratio, and 25-OH vitamin D3 levels. Here, we examined the association between VDR rs2228570 polymorphism and PD risk in a Chinese population. A total of 940 subjects were included in this study, which consisted of 470 patients with sporadic PD (mean age: 62.65 ± 9.34 years) and 470 healthy control subjects (mean age: 62.70 ± 9.42 years). A TaqMan genotyping assay was applied to identify VDR rs2228570 polymorphism. The Hardy-Weinberg Equilibrium (HWE) was calculated for both groups with a Chi-square (χ2) test. The sample power was calculated with Power V3.0. The crude odds ratios (ORs) and 95 % confidence intervals (CIs) for sporadic PD in relation to VDR rs2228570 polymorphism were calculated using a logistic regression analysis. The minor A allele frequency was 0.42 and 0.48 in the control and PD groups, respectively. A allele carriers of rs2228570 were associated with an increased overall risk of PD as well as early-onset PD (EOPD) in the allele and additive genetic models. Stratification analyses showed similar results in male subjects in the allele and additive genetic models, but only in the additive genetic model in female subjects. In conclusion, our study suggests that the VDR rs2228570 A allele is associated with an increased risk of PD in a Chinese population. Further investigations with larger sample sizes with consideration of gene-gene and gene-environment interaction are needed to further elucidate the role of vitamin D receptors in the development of PD.

LMO1 polymorphisms and the risk of neuroblastoma: Assessment of meta-analysis of case-control studies.

Neuroblastoma (NB), a neuroendocrine tumour, is one of the most prevalent cancers in children. The link between LMO1 polymorphisms and NB has been investigated by several groups, rendering inconclusive results. Here, with this comprehensive systematic review and up‐to‐date meta‐analysis, we aim to distinctively elucidate the possible correlation between LMO1 polymorphisms and NB susceptibility. Eligible studies were systematically researched and identified using PubMed, Web of Science and Scopus databases up to 10 February 2019. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of the associations. Our findings revealed that rs110419 and rs2168101 polymorphisms were significantly associated with a decreased risk of NB in all genetic models. In addition, the rs4758051 variant appeared protective against NB in homozygous, dominant and allele genetic models, whereas the rs10840002 variant markedly decreased the risk of NB in the allele model. In contrast, the rs204938 polymorphism showed a positive association with NB susceptibility in allele genetic models. In summary, our meta‐analysis is the first to provide clear evidence of an association between specific polymorphisms of LMO1 and susceptibility to NB. Of note, additional larger well‐designed studies would be helpful to further evaluate and confirm this association.

Association between interleukin-8 rs4073 polymorphism and prostate cancer: A meta-analysis

Interleukin-8 (IL-8) is an inflammatory cytokine and plays important role in development of cancers. We conducted a meta-analysis to explore the association between IL-8 rs4073 polymorphism and risk of prostate cancer. PubMed, Embase, Cochrane Library, and Web of Science databases were searched for only case-control studies published before February 2019. The methodological quality assessment of included studies was performed based on Newcastle-Ottawa Quality Scale (NOS). Based on the heterogeneity, we conducted a meta-analysis using random-effect models. Pooled odds ratios (ORs) with a 95% confidence interval (CI) were calculated using the allele (T vs. A), homozygous (TT vs. AA), heterozygous (TA vs. AA), dominant (TT+TA vs. AA), and recessive (TT vs. TA+AA) genetic models to assess the strength of the relationship between IL-8 rs4073 polymorphism and prostate cancer risk. In addition, the stability of our analysis was evaluated by heterogeneity, sensitivity, subgroup of ethnicity and study design, and publication bias analysis. We included 6 case-control studies with a total of 1752 cases and 1982 controls. Significantly higher prostate cancer risk of 1.12 (95% CI=1.01-1.25), 1.26 (95% CI=1.03-1.55), and 1.20 (95% CI=1.02-1.41) were found for the allele, homogeneous, and recessive model, respectively. Though there was no statistical association with other genetic models in our meta-analyses, a tendency of higher prostate cancer risk was observed in all five genetic models. The major findings of this meta-analysis suggested that IL-8 rs4073 polymorphism is significantly associated with risk of prostate cancer.

The genetic variants in calcium signaling related genes influence anti-tuberculosis drug induced liver injury: A prospective study.

Although many genetic variants related to anti-tuberculosis drug induced liver injury (ATDILI) have been identified, the prediction and personalized treatment of ATDILI have failed to achieve, indicating there remains an area for further exploration. This study aimed to explore the influence of single nucleotide polymorphisms (SNPs) in Bradykinin receptor B2 (BDKRB2), Teneurin transmembrane protein 2 (TENM2), transforming growth factor beta 2 (TGFB2), and solute carrier family 2 member 13 (SLC2A13) on the risk of ATDILI.The subjects comprised 746 Chinese tuberculosis (TB) patients. Custom-by-design 2x48-Plex SNPscanTM kit was employed to genotype 28 selected SNPs. The associations of SNPs with ATDILI risk and clinical phenotypes were analyzed according to the distributions of allelic and genotypic frequencies and different genetic models. The odds ratio (OR) with corresponding 95% confidence interval (CI) was calculated.Among subjects with successfully genotyped, 107 participants suffered from ATDILI during follow-up. In BDKRB2, patients with rs79280755 G allele or rs117806152 C allele were more vulnerable to ATDILI (PBonferronicorrection = .002 and .03, respectively). Rs79280755 increased the risk of ATDILI significantly whether in additive (OR = 3.218, 95% CI: 1.686–6.139, PBonferroni correction = .003) or dominant model (PBonferroni correction = .003), as well as rs117806152 (Additive model: PBonferroni correction = .05; dominant model: PBonferroni correction = .03). For TENM2, rs80003210 G allele contributed to the decreased risk of ATDILI (PBonferroni correction = .02), while rs2617972 A allele conferred susceptibility to ATDILI (PBonferroni correction = .01). Regarding rs2617972, significant findings were also observed in both additive (OR = 3.203, 95% CI: 1.487–6.896, PBonferroni correction = .02) and dominant model (PBonferroni correction = .02). Moreover, rs79280755 and rs117806152 in BDKRB2 significantly affected some laboratory indicators. However, no meaningful SNPs were observed in TGFB2 and SLC2A13.Our study revealed that both BDKRB2 and TENM2 genetic polymorphisms were interrogated in relation to ATDILI susceptibility and some laboratory indicators in the Western Chinese Han population, shedding a new light on exploring novel biomarkers and targets for ATDILI.

Association of MTHFR C677T polymorphism and type 2 diabetes mellitus (T2DM) susceptibility.

IntroductionMethylenetetrahydrofolate reductase (MTHFR) is essential in mediating folate metabolism, and thus plays an important role in diabetes and diabetic complications. MTHFR C677T (rs1801133 C>T) polymorphism has been proposed to be linked with type 2 diabetes mellitus (T2DM) susceptibility. However, the conclusions are inconsistent. Therefore, we rechecked their linkage aiming to obtain a more reliable estimation by performing an updated meta‐analysis.MethodsWe searched electronic databases PubMed, EMBASE, CNKI, and Wanfang to obtain studies updated to October 2019.ResultsAfter carefully screening, we finally incorporated 68 studies with 10,812 cases and 8,745 controls. The genotype frequency of C677T polymorphism was analyzed pooled to generate odds ratios (ORs) and 95% confidence intervals (CIs). Pooled results presented that MTHFR C677T polymorphism was significantly associated with T2DM under homozygous (OR = 1.64, 95% CI = 1.39–1.94), heterozygous (OR = 1.38, 95% CI = 1.20–1.59), recessive (OR = 1.41, 95% CI = 1.23–1.61), dominant (OR = 1.47, 95% CI = 1.27–1.70), and allele (OR = 1.37, 95% CI = 1.23–1.52) genetic models. Stratified analysis demonstrated that C677T genotype was associated with T2DM in Asian populations, but not Caucasian and African populations.ConclusionOur results indicated that MTHFR C677T polymorphism confers to T2DM, especially in Asian populations. Much more large‐scale case–control studies are needed to strengthen such conclusion in the future.

Association of Genetic Polymorphisms of GREM1 Gene with Susceptibility to Non-Syndromic Cleft Lip with or without Cleft Palate in an Iranian Population

Background: Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is common congenital birth anomaly with multifactorial etiology. The GREM1 gene has been proposed to play a role in oral clefts development.Objective: The aim of the present study was to evaluate the correlation between GREM1 polymorphisms and the risk of NSCL/P in an Iranian population.Methods: Genotyping of rs7162202, rs12915554, rs3743105, rs1129456, and rs10318 polymorphisms of GREM1 gene in 150 NSCL/P and 152 healthy subjects was determined by the PCR‐RFLP or T-ARMS-PCR.Results: The findings showed that the rs12915554 variant significantly increased the risk of NSCL/P in heterozygous (OR = 4.20, 95%CI = 2.46–7.11, p < 0.0001, AC vs AA), and allele (OR = 3.17, 95%CI = 2.00–5.08, p < 0.0001, C vs A) genetic models. The rs3743105 polymorphism was correlated with reduced risk of NSCL/P in heterozygous (OR = 0.49, 95%CI = 0.29–0.83, p = 0.008, AG vs GG) and dominant (OR = 0.54, 95%CI = 0.33–0.89, p = 0.018, GA + AA vs GG) genetic models. The rs1129456 variant was positively associated with the risk of NSCL/P in heterozygous (OR = 2.91, 95%CI = 1.12–7.38, p = 0.028, AT vs AA) and allele (OR = 2.80, 95%CI = 2.80–6.95, p = 0.031, T vs C). The rs10318 polymorphism significantly reduced NSCL/P risk in homozygous (OR = 0.20, 95%CI = 0.06–0.67, p = 0.013, TT vs CC), dominant (OR = 0.57, 95%CI = 0.36–0.91, p = 0.019, CT + CC vs CC), recessive (OR = 0.24, 95%CI = 0.07–0.76, p = 0.031, TT vs CT + CC), and allele (OR = 0.57, 95%CI = 0.38–0.84, p = 0.005, T vs C). No correlation was observed between rs7162202 polymorphism and NSCL/P.Conclusion: The findings support that GREM1 polymorphisms are involved in NSCL/P susceptibility in an Iranian population.