Heterozygous Genetic Models Research Articles

Correlation of BARD1 gene polymorphisms with risk of neuroblastoma: a meta-analysis

BRCA1-associated RING domain protein 1 (BARD1) gene polymorphisms may be associated with neuroblastoma (NB) susceptibility. However, the results remain controversial. Relevant studies were identified by searching PubMed, Web of Science, Embase, China National Knowledge Infrastructure databases up to March 5, 2023. The strength of the association between BARD1 polymorphisms and susceptibility of NB was assessed by calculating odds ratios (ORs) and 95% confidence intervals (95% CIs) through the fixed- or random-effects model. Eight articles involving 12 studies were finally included. We found that rs6435862 T > G, rs3768716 A > G, rs17487792 C > T and rs7587476 C > T variant increase the risk of NB in allelic, dominant, recessive, homozygous and heterozygous genetic models, while rs7585356 G > A variant appeared protective against NB. When stratified by ethnicity, subgroup analysis indicated that the above association remained significant in Caucasian populations in all genetic models, except for rs7585356G > A polymorphism in Asians. In Asian populations, we found the similar results in the allelic and dominant model of rs6435862 T > G, rs3768716 A > G, rs17487792 C > T and rs7587476 C > T as in Caucasians, while there lacked a significant association in the other three model. In addition, rs7585356 G > A was not associated with an increased risk of NB in the Asian population. After Bonferroni correction, significant associations for rs7585356 G > A disappeared in both Asian and Caucasian populations, with no significant association found for rs7587476 in the allelic and dominant models among Asians. BARD1 polymorphisms might be significantly associated with NB susceptibility. It is crucial that these finding should be further confirmed through extensive and well-planned studies.

The relationship between polymorphism of IGF2BP2 gene rs4402960 and risk of pan-cancer: a meta-analysis and a bioinformatics analysis

Objective To conduct a meta-analysis and a bioinformatics analysis to assess the relationship between IGF2BP2 gene polymorphism and pan-cancer risk. Methods PubMed, EMBASE, and Web of Science were conducted to literature searches. The heterogeneity test was used in five genetic models. Odds ratios (OR), 95% confidence intervals (CI), and p-values were used to evaluate the combined effects of various genetic models. Subgroup analysis and Meta-regression analysis were used to analyze the characteristics of heterogeneity. Sensitivity analysis and publication bias were also performed. Transcriptomic information on IGF2BP2 was downloaded and analyzed from the TCGA and GTEx databases. GEPIA (http://gepia.cancer-pku.cn/) was performed to analyze the relationship between IGF2BP2 expression and cancer tissue. Results This meta-analysis contained 7 case–control studies, with 5,908 cases and 7,890 controls. There were significant differences in the heterozygous genetic model of IGF2BP2 gene rs4402960 polymorphism (OR = 1.080, 95% CI = 1.003–1.163, p = 0.041). In subgroup analysis based on ethnicity, There was a statistical significant association in Chinese (heterozygous: OR = 1.110, 95% CI = 1.010–1.220, p = 0.030). Bioinformatics analysis found that IGF2BP2 was over-expressed in pan-cancer (p < 0.01). In addition, the Kaplan-Meier estimate showed that there is statistical significance of OS between the low and high IGF2BP2 TPM groups in Lung adenocarcinoma (p <0.001). Conclusions To sum up, IGF2BP2 gene polymorphism may be related to cancer risk. IGF2BP2 has diagnostic value in the diagnosis and treatment of pan-cancer.

The impact of folate pathway variants on the outcome of methotrexate therapy in rheumatoid arthritis patients.

There are currently no validated criteria that entirely explain or predict response to methotrexate (MTX) treatment in rheumatoid arthritis (RA). We tried to identify the connection between three variants (RFC1 G80A (rs1051266), TYMS 2R/3R (rs34743033), and ATIC C347G (rs2372536)) in the folate pathway of MTX metabolism and the response to MTX monotherapy in a cohort of RA cases. A prospective study on 100 RA patients on MTX monotherapy was performed. Disease activity was measured at the start of treatment and 6months after treatment with MTX. The patients were then split into two groups: those who responded to the treatment and those who did not. The molecular genetic study for the RFC1 (G80A) variant was employed via the PCR-restriction fragment length polymorphism (PCR-RFLP) technique, the ATIC (C347G) variant was performed using TaqMan allelic discrimination real-time PCR, and the tandem repeat sequences of TYMS (2R/3R) were amplified by conventional PCR and detected by agarose gel electrophoresis. The genotype distribution of RFC-1 (G80A) showed significant variations among non-responders and responders in the recessive genetic model. A significant difference was found in TYMS (2R/3R) in the dominant and heterozygous genetic models. However, ATIC (C347G) genotype frequency did not exhibit substantial link with drug response in all genetic models. Furthermore, the genotype and allele rates of the analyzed variants did not show any significant association with adverse events in all genetic models. The 80AA genotype of RFC-1 G80A and the 2R/3R or 3R/3R genotypes of TYMS 2R/3R are more vulnerable to the good consequences of MTX therapy. Key Points • Current recommendations support the gold standard role of MTX as a first-line monotherapy for RA patients. However, up to 40% of RA patients do not respond or exhibit partial response to MTX. • Persistent disease activity due to treatment unresponsiveness will affect the long-term outcomes in RA patients. • We aimed, through molecular genetic study, to identify the connection between three variants in the folate pathway of MTX metabolism and the response to methotrexate monotherapy in a cohort of RA patients.

Systematic evaluation of the association between a missense variant in XRCC3 gene splicing site and the pathogenesis of ovarian cancer.

The effects and underlying mechanism of XRCC3 rs861539 on the risk of ovarian cancer (OC) are still unclear. Therefore, a meta-analysis of 10 studies containing 6,375 OC cases and 10,204 controls was performed for this topic. Compared with GG genotype, GA + AA genotypes could significantly decrease the OC risk, odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were 0.89 (0.83-0.95) and P=0.001, and 0.88 (0.82-0.95) and P=0.001 under the dominant and heterozygous genetic models. Compared with G allele, rs861539 A could significantly reduce the OC risk, OR and its corresponding 95% CI was 0.94 (0.89-0.98) and P=0.007. By subgroup analysis in ethnicity, protective effects on OC risk in Caucasians were observed (the dominant model: OR = 0.88, 95% CI = 0.82-0.94, P<0.001; the heterozygous model: OR = 0.87, 95% CI = 0.81-0.94, P<0.001; the allelic model: OR = 0.93, 95% CI = 0.88-0.97, P=0.003; the homozygous model: OR = 0.89, 95% CI = 0.80-0.98, P=0.024). The authenticity of positive association findings was further confirmed by trial sequential analysis (TSA) and false-positive report probability (FPRP) analysis. The subsequent functional analysis revealed that rs861539 could regulate the post-transcriptional expression of XRCC3 by changing the activity of putative splice sites and types of splicing factors. rs861539 also may act as an expression Quantitative Trait Loci (eQTL) affecting the expression of genes such as XRCC3, MARK3, APOPT1, etc., and has an impact on the structure of XRCC3.

Rs719725 Polymorphism and Colorectal Cancer Susceptibility: A Meta-analysis.

Many studies have suggested an association between 9p24 rs719725 polymorphism and colorectal cancer (CRC) risk, but with inconsistent results. This meta-analysis aimed to summarise the overall association of rs719725 polymorphism with CRC risk. Nine eligible articles with 21 case-control studies (16015 CRC patients and 19341 controls) on the rs719725 polymorphism and CRC susceptibility from four electronic databases (Web of Science, PubMed, SinoMed, and EMBASE) were retrieved and analysed. The association was evaluated with publication bias, pooled OR (odds ratio), and corresponding 95% CI (confidence interval). The pooled results indicated a significant association between the increased CRC risk and rs719725 polymorphism in dominant ([OR] 1.220, [95%CI] 1.161-1.282), recessive (1.166, 1.102-1.234), allele (1.142, 1.102-1.184), homozygous (1.306, 1.212-1.406), and heterozygous (1.18, 1.129-1.234) genetic models. The ethnicity-stratified analyses found a consistently significant association. In the stratification analysis with the source of controls, such significant association was also detected amid the population-based studies under the four former genetic models. Taken together, this meta-analysis indicates that rs719725 genetic variants are associated with an increased risk of CRC among Caucasians and population-based studies. Further relevant research is warranted to confirm these findings. Key Words: Colorectal cancer, rs719725, Polymorphism, Meta-analysis, Stratification analysis.

The Association of Methylenetetrahydrofolate Reductase (MTHFR) A1298C Gene Polymorphism with Susceptibility to Diabetic Nephropathy: A Meta-Analysis.

This meta-analysis was conducted to investigate the association between MTHFR A1298C polymorphism and susceptibility to diabetic nephropathy. PubMed, Embase, Web of Science, Cochrane Library, China national knowledge infrastructure (CNKI) and China Wanfang database were searched for studies on the association between MTHFR A1298C single nucleotide polymorphism and susceptibility to diabetic nephropathy until May 2022. Data were analyzed by Stata 15.0 software. Odds ratio (OR) was used as the effect size. A total of 7 articles were identified, including 1287 cases in the diabetic nephropathy group and 1431 cases in the control group. The pooled OR of allele C at MTHFR A1298C was 1.28 (95% CI: 1.02-1.59, p=0.03) compared with allele A. The pooled OR values of dominant, and heterozygous genetic models were 1.45 (95% CI: 1.13-1.86), and 1.42 (95% CI: 1.19-1.70), respectively, and the differences were all statistically significant. There was no statistical significance in the recessive (OR=1.06, 95% CI: 0.62-1.82), and homozygous gene inheritance models (OR=1.29, 95% CI: 0.72-2.31). In conclusion, MTHFR A1298C polymorphism is associated with susceptibility to diabetic nephropathy. Allele C, genotype CC+AC, and AC at MTHFR A1298C locus can increase the risk of diabetic nephropathy.

Association of the Transcription Factor 7-Like 2 (TCF7L2) rs7903146 Polymorphism with the Risk of Diabetic Nephropathy: A Meta-Analysis.

Transcription factor 7-like 2 (TCF7L2) polymorphism plays an essential role in the occurrence and development of patients living with diabetes, but the current conclusions are inconsistent on the relationship between TCF7L2 polymorphism and the risk of diabetic nephropathy. This meta-analysis aims to explore the exact association between TCF7L2 rs7903146 locus polymorphism and susceptibility to diabetic nephropathy. PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and China Wanfang databases were searched for studies on the relationship between single nucleotide polymorphism at TCF7L2 rs7903146 locus and susceptibility to diabetic nephropathy until January 10, 2022. The data were analyzed by Stata 15.0 software. A total of 7 articles were included, covering 1443 patients with diabetic nephropathy and 2129 diabetic non-nephropathy patients. The results showed that allele C at TCF7L2 rs7903146 locus, compared to allele T, the pooled odds ratio (OR)=0.69 (95% CI: 0.56-0.85, p≤0.05). In the dominant gene inheritance model, recessive gene inheritance model, homozygous genetic model, and heterozygous genetic model, the pooled OR was 0.47 (95% CI: 0.36-0.61), 0.63 (95% CI: 0.54-0.73), 0.39 (95% CI: 0.29-0.51), and 0.59 (95% CI: 0.45-0.78), respectively, and the differences were statistically significant. In conclusion, TCF7L2 rs7903146 polymorphism is associated with susceptibility to diabetic nephropathy. Allele T and genotype TT can increase the risk of diabetic nephropathy.

Association between IL-10 rs3024505 and susceptibility to inflammatory bowel disease: A systematic review and meta-analysis.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease that affects the small intestine, colon, and rectum. We evaluated associations between the interleukin 10 (IL-10) rs3024505 polymorphism and IBD, ulcerative colitis (UC), and Crohn's disease (CD) by meta-analysis. All peer-reviewed manuscripts concerning the relationship between IL-10_rs3024505 and IBD identified by searing the PubMed, Cochrane Library, EMBASE, and Chinese Medical Database were examined. The association between IL-10_rs3024505 and IBD was evaluated in allele (AG), recessive (RG), dominant (DG), homozygous (HMG), and heterozygous (HTG) genetic models. Associations were also conducted on IBD subtypes, CD and UC, and ethnicity (Non-Europeans and Europeans) subgroups. The meta-analysis included 13 studies, 8552 cases (IBD patients), and 12,830 healthy controls. Subgroup analysis of IBD (UC and CD) revealed heterogeneity in AG, DG, and HTG but no heterogeneity in RG or HMG. Moreover, AG, DG, and HTG did not show publication bias in IBD, CD, or UC, but RG and HMG exhibited publication bias. No heterogeneity and no publication bias were found among the five genetic models by a subgroup analysis of Non-Europeans and European ethnicities. The minor allele(T) of rs3024505 was significantly related to IBD: 1.37 (1.30-1.45) for AG, 2.06 (1.74-2.45) for RG, 1.39 (1.27-1.52) for DG, 2.25 (1.89-2.67) for HMG, and 1.32 (1.23-1.40) for HTG (all P<0.00001). In the subgroup analysis of ethnicity, there was a significant effect of rs3024505 on IBD in Europeans but not non-Europeans: 1.38 (1.31-1.46) for AG, 2.07 (1.73-2.48) for RG, 1.39 (1.31-1.49) for DG, 2.26 (1.89-2.71) for HMG, and 1.33 (1.24-1.42) for HTG in Europeans (all P<0.00001). Sensitivity analysis showed no dominant study in Europeans, but one study had a dominant impact in Non-Europeans. In conclusion, IL-10_rs3024505 polymorphism confers susceptibility to CD and UC in Europeans, but its impact should have conducted more studies in Non-Europeans.

The CYP19A1 (TTTA)n Repeat Polymorphism May Affect the Prostate Cancer Risk: Evidence from a Meta-Analysis.

Abnormal aromatase (CYP19A1) expression may participate in prostate cancer (PCa) carcinogenesis. However, the results of studies on the CYP19A1 gene polymorphisms and PCa are conflicting. This meta-analysis aimed to systematically evaluate the associations between the CYP19A1 Arg264Cys polymorphism and the (TTTA)n repeat polymorphism and PCa. Electronic databases (PubMed, EmBase, ScienceDirect, and Cochrane Library) were comprehensively searched to identify eligible studies. The strength of the association between the Arg264Cys polymorphism and PCa was assessed by pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) in allelic, dominant, recessive, homozygous, and heterozygous genetic models. To analyze the impact of the (TTTA)n repeat polymorphism, we sequentially took the N-repeat allele (where N equals 7,8,10,11,12, and 13) as the minor allele and the sum of all the other alleles as the major allele. The ORs and 95% CIs were calculated in the allelic model; this analysis was performed individually for each repeat number. Pooled estimates of nine studies addressing the Arg264Cys polymorphism indicated that this polymorphism was not associated with PCa risk in the overall population or in the Caucasian or Asian subgroups. The 8-repeat allele in the (TTTA)n repeat polymorphism increased PCa risk in the overall population (OR = 1.34, 95% CI = 1.14–1.58, p = .001) and in the subgroup with population-based (PB) controls (OR = 1.41, 95% CI = 1.13–1.74, p = .002) as well as in the subgroup using capillary electrophoresis to identify this polymorphism (OR = 1.34, 95% CI = 1.09–1.65, p = .006).The meta-analysis indicated that the CYP19A1 (TTTA)n repeat polymorphism, but not the Arg264Cys polymorphism, may affect PCa risk.

IL-4 rs2243250 polymorphism associated with susceptibility to allergic rhinitis: a meta-analysis.

Objective: The relationship between IL-4 rs2243250 polymorphism and the risk of allergic rhinitis is not clear at present. The present study aims to evaluate the exact association between IL-4 rs2243250 polymorphism and susceptibility to allergic rhinitis by a meta-analysis.Methods: The studies about IL-4 rs2243250 polymorphism associated with susceptibility to allergic rhinitis were searched using PubMed, Excerpta Medica Database (EMBASE), Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI) and China Wanfang databases. The last search time was on March 1, 2021. Data analysis was performed using Stata 15.0 software.Results: Nine documents were enrolled, from which 1709 patients with allergic rhinitis were included. Among them, six genotype frequencies in the control group conformed to Hardy–Weinberg Equilibrium (HWE). The meta-analysis of all included studies showed significant heterogeneity of each gene model. After omitting the studies whose genotype frequency in the control group did not meet the requirements of HWE, no significant heterogeneity was found in each gene model. The meta-analysis results of the control group genotypes in line with the HWE showed statistically significant differences in the pooled odds ratio (OR) of allele model (T vs. C), recessive model (TT vs. TC+CC) and homozygous model (TT vs. CC), which were 1.19 (95%CI: 1.04–1.35), 1.28 (95%CI: 1.06–1.55) and 1.56 (95%CI: 1.13–2.17), respectively. No statistically significant difference was observed in dominant and heterozygous genetic models.Conclusion: IL-4 rs2243250 single nucleotide polymorphism associated with susceptibility to allergic rhinitis, allele T and genotype TT could increase the risk of allergic rhinitis.

IKZF1 Rs4132601 Polymorphism and Susceptibility to Acute Lymphocytic Leukemia in Children: A Meta-analysis.

Many studies have shown that IKAROS family zinc finger 1 (IKZF1) rs4132601 polymorphism is strongly linked to acute lymphoblastic leukemia (ALL) in children, but their conclusions have been inconsistent. This meta-analysis is set out to investigate the association between IKZF1 rs4132601 polymorphism and its susceptibility to childhood ALL. On the basis of inclusion criteria, PubMed, EMBASE, Web of Science, CNKI, China Wanfang, VIP, and other databases were searched from the time of the establishment of the library database to December 2019 for all case-control studies. Stata 15.0 was applied for meta-analysis to calculate the combined odds ratio (OR) value and 95% confidence interval (CI) of each genotype at IKZF1 rs4132601. Subgroup analysis done by ethnicity, sensitivity analysis, and publication bias assessment was further performed. Nine pieces of literature was included in this meta-analysis, including 2281 children with ALL and 2923 controls. There were significant differences in the allelic model (T vs. G: combined OR=0.75, 95% CI: 0.68-0.82, P<0.05) in both Asian and Caucasian children. In addition to this, there were statistically significant differences in the dominant, homozygous and heterozygous genetic model in both Asian and Caucasian children. The difference was significant in the recessive genetic model (TT vs. TG+GG: combined OR=0.75, 95% CI: 0.67-0.84) in Caucasian children, but not in Asian children (combined OR=0.85, 95% CI: 0.70-1.04, P>0.05). There is a strong correlation between IKZF1 rs4132601 polymorphism and ALL in children. Compared with the G allele, T alleles can lower the risk of childhood ALL, and TT, TT+TG and TG genotypes can also reduce the risk of ALL in children.

FVII gene R353Q polymorphism and coronary heart disease: a meta-analysis including 3258 subjects.

The coagulation factor VII (FVII) gene R353Q polymorphism is suggested to be relevant to the coronary heart disease (CHD) susceptibility. However, the results of separate studies are not consistent with one another. A meta-analysis including 3258 participants from nine studies was conducted to investigate the relationship between the FVII gene R353Q polymorphism and the CHD in the Chinese population. The fixed-effect models were used to assess the pooled odds ratios (ORs) and their corresponding 95% confidence intervals. A significant association was observed between the FVII gene R353Q polymorphism and the CHD in the Chinese population under allelic (OR 1.34, 95% CI 1.10-1.65, P = 0.004), dominant (OR 0.68, 95% CI 0.55-0.85, P = 0.0006), and heterozygous (OR 0.68, 95% CI 0.55-0.85, P = 0.0007) genetic models. The FVII gene R353Q polymorphism was significantly correlated with the CHD susceptibility in the Chinese population. Persons with the R allele of the FVII gene R353Q polymorphism might have greater CHD risk than others.

Angiotensinogen M235T polymorphism and susceptibility to hypertrophic cardiomyopathy in Asian population: A meta analysis.

Objective:To explore the relationship between the polymorphism of angiotensinogen gene (AGT) M235T and susceptibility to hypertrophic cardiomyopathy (HCM) in Asian population by meta-analysis.Methods:PubMed, Embase, Web of Science, Cochrane library, CNKI, Wan Fang, and other databases were searched to collect the literature about AGT M235T polymorphism and HCM from the inception to March 1, 2020. The Newcastle-Ottawa Scale (NOS) checklist was uesd to perform independent literature review and study quality assessment. Data was analyzed by Stata 15.0 software.Results:The results showed that, except for the recessive genetic model (TT vs MT+MM: OR = 1.27, 95%CI: 1.05–1.53), in the other four genetic models, the M235T polymorphism had no significant correlation with the risk of HCM (T vs M: OR = 1.17, 95%CI: 0.88–1.57; TT+MT vs MM: OR = 1.13, 95%CI: 0.55–2.33; TT vs MM: OR = 1.25, 95%CI: 0.60–2.59; TM vs MM: OR = 0.95, 95%CI0.5–1.82). The results of subgroup analysis showed that, except for the heterozygous genetic model, in the other four genetic models, M235T polymorphism was significantly associated with sporadic hypertrophic cardiomyopathy (SHCM), but not with familial hypertrophic cardiomyopathy (FHCM) (p > 0.05).Conclusion:M235T polymorphism in Asians is associated with HCM, especially SHCM. Heterozygotes increase the risk of patients with SHCM.

Association Between FokI Polymorphism of Vitamin D Receptor Gene and Lumbar Spine Disc Degeneration: A Systematic Review and Meta-Analysis.

The aim of the present meta-analysis was to explore the association between FokI polymorphism of the vitamin D receptor gene and lumbar spine disc degeneration. The search was performed in PubMed, Scopus, and Web of Science databases up to January 2020. The authors selected nine studies comprising a total of 1549 cases and 1672 controls. The association analysis included the allelic, dominant, recessive, homozygous, and heterozygous genetic models. Odds ratios with 95% confidence intervals were used to evaluate the association. The Newcastle-Ottawa Scale was used to measure the quality of the studies included in the analyses; a cut-off of 6 stars was applied. This meta-analysis indicated that FokI polymorphism is significantly associated with lumbar degenerative disc disorder and disc herniation in the homozygous (odds ratio, 1.77; 95% confidence interval, 1.23-2.54; Z test P = 0.002, Q test P = 0.416) and recessive (odds ratio, 1.53; 95% confidence interval, 1.23-1.90; Z test P < 0.000, Q test P = 0.224) models. This study indicates that the vitamin D receptor gene FokI polymorphism may be correlated with the risk of developing a lumbar degenerative disc disorder and disc herniation. However, the small sample population studied and the lack of an evaluation of environmental factors must be taken as limitations in the present meta-analysis.

Rs10490924 surrounding HTRA1/ARMS2 regulates the susceptibility of age-related macular degeneration

Multiple studies have assessed the contribution of rs10490924 on chromosome 10q26 surrounding HTRA1/ARMS2 gene to age-related macular degeneration (AMD) risk. However, the causal allele at this locus is still inconclusive. In this meta-analysis, we systematically characterized the potential association between rs10490924 polymorphism and AMD risk. Data available from 12 case-control studies, including a total of 5244 cases and 2755 controls in three different ethnic populations, were used to evaluate the correlation between rs10490924 G/T polymorphism (Ala69Ser) and AMD risk. In overall populations, the results indicated the Ala69Ser polymorphism was significantly associated with AMD under allelic (OR = 0.35, 95% CI = 0.30–0.40), homozygous (OR = 0.12, 95%CI = 0.09–0.17), dominant (OR = 0.18, 95%CI = 0.14–0.24), recessive (OR = 0.33, 95%CI = 0.28–0.39), and heterozygous genetic models (OR = 0.26, 95% CI = 0.21–0.33). Similar results were observed in subgroup analysis. This meta-analysis suggests that rs10490924 (Ala69Ser) polymorphism was significantly associated with the susceptibility of AMD in all ethnicities, Ala69 carriers are resistant to AMD risk.

Gene polymorphism associated with angiotensinogen (M235T), endothelial lipase (584C/T) and susceptibility to coronary artery disease: a meta-analysis.

Objective: To explore the association between the variant M235T locus of angiotensinogen (AGT) gene, 584C/T locus of Endothelial lipase (EL) gene, and coronary artery disease (CAD) by meta-analysis.Methods: The case–control studies on the association between AGT/EL gene polymorphism and CAD were collected through searching PubMed, Excerpta Medica Database (EMBASE), Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases up to 1 March 2020. Stata 15.0 software was used for analysis.Results: A total of 29 articles met the inclusion criteria. After analyzing, it was found that the M235T polymorphism of AGT gene was associated with the occurrence of CAD. In the allele model (T vs. M), OR = 1.38 (P<v0.05). In other heredity, there was also statistical significance. Subgroup analysis indicated that except the heterozygous genetic model of the Chinese population, other genetic models of the Caucasian and Chinese population were also statistically significant. The 584C/T polymorphism of EL gene was associated with the occurrence of CAD, with OR = 0.83 (P<0.05) in the allele model (T vs. C) and OR = 0.80 (P<0.05) in the dominant gene model. Also, in the allele model of Caucasian subgroup, OR = 0.83 (P<0.05), while in Asian subgroup, there was no statistically significant genetic model.Conclusion: AGT M235T and EL 584C/T polymorphisms are associated with CAD susceptibility. The genotype TT, TC or allele T of AGT M235T and genotype CC or allele C of EL 584C/T might be the genetic risk factors for the development of CAD.

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.

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.

Meta-Analysis of CTLA-4 +49 Gene Polymorphism and Susceptibility to Graves' Disease.

Literature searches were performed in PubMed, Embase, Web of Science, China National Knowledge Infrastructure, China Wanfang, and other databases for data on the correlation between polymorphisms of CTLA-4 +49A/G and GD risk. The end date for publications was May 2020. Stata 15.0 software was used for data analysis. A total of 33 papers were included, covering 8,555 cases and 9,533 controls. The results showed that the CTLA-4 +49 allele G compared to allele A, odds ratio (OR) = 1.62, 95% CI [1.56, 2.09]. In the dominant, recessive, homozygous, and heterozygous genetic models, comparing the GD group and the control group, the combined OR was 1.81, 95% CI [1.56, 2.09]; 1.91, 95% CI [1.66, 2.21]; 2.75, 95% CI, [2.21, 3.41]; and 1.49, 95% CI [1.29, 1.71], respectively. When it was analyzed by dividing genetic models into subgroups according to ethnicity and published year, the data the of genetic model in each subgroup were also statistically significant. The CTLA-4 +49A/G polymorphism was strongly associated with genetic susceptibility to GD. Allele G, genotypes GG, GG + GA, and GA are correlated with an increase in the risk of GD.

Association between polymorphisms in interleukin-18 promoter and risk of coronary artery disease: a meta-analysis.

Background: Previous studies have explored associations between interleukin-18 (IL-18) promoter polymorphisms and coronary artery disease (CAD). However, the results were controversial. We conducted a meta-analysis to clarify the association between the two polymorphisms and CAD risk. Methods: We searched English and Chinese databases and calculated the odds ratio (OR) and 95% confidence interval (CI) to estimate whether there are genetic associations between IL-18 promoter polymorphisms and the risk of CAD. All relevant studies were screened and meta-analyzed using STATA 15.0. Results: A total of 15 studies, including 12 studies for -137 G/C and 9 studies for -607 C/A, were identified for the meta-analysis. For -137 G/C, the results showed a significantly reduced risk of CAD in the dominant model (OR = 0.85) and heterozygous model (OR = 0.88) in the overall analysis. However, in subgroup analysis, decreased CAD risks were only observed in Asian populations for heterozygous genetic models. For -607 C/A, the overall OR revealed a reduced risk of CAD in all five genetic models (allelic, OR = 0.78; recessive, OR = 0.75; dominant, OR = 0.68; homozygous, OR = 0.61; heterozygous, OR = 0.72). In subgroup analysis, reduced CAD risk was also found in five genetic models of the Asian population. We also found that the IL-18 polymorphisms were correlated with myocardial infarction (MI) and multivessel (MV) disease. Conclusion: Our results suggested that the -137 polymorphism and -607 polymorphism in the IL-18 promoter were negatively associated with CAD, especially in the Asian population. In addition, some genetic models were correlated with the severity of CAD.