Recessive Gene Model Research Articles

O102 RELATIONSHIP BETWEEN AGTR1 (c.1166 A>C) POLYMORPHISMS AND KIDNEY INJURY IN HYPERTENSION

Background: High blood pressure is the main cause of cardiovascular diseases. Kidney damage is one of the most common organ secondary damage to hypertension. The study of hypertension gene polymorphisms is an important means of precision treatment of primary hypertension. Objectives: The objective of this study was to explore the relationship between AGTR1 (c.1166 A>C) gene polymorphisms and hypertension combined with kidney damage, while exploring the relationship between codominant, dominant and recessive gene model and hypertension with kidney injury and the susceptibility of different genotypes to hypertension with kidney injury. Methods: The distribution of AGTR1 polymorphism in the AGTR1 in hypertensive patients (hypertension group, 292 patients) and hypertension with kidney injury patients (44 patients) were detected and compared by PCR-melting curve method. Results: The genotype distribution of hypertension and combined groups met Hardy-Weinberg equilibrium (p > 0.05); the distribution difference between the three genotypes was statistically significant (p < 0.05), the codominant, dominant and recessive distribution frequency of genotypes (p < 0.05), and no difference between A allele and C allele (p > 0.05). Conclusions: Our study identified the relationship of AGTRA (c.1166 A>C) with hypertension combined with renal injury, and compared the susceptibility of different genetic models, which may provide novel targets for precision gene therapy of hypertension.

Association of ADAMTS-5 gene polymorphisms with the susceptibility to knee osteoarthritis in a Chinese Han population

BackgroundOsteoarthritis (OA) is the most prevalent type of arthritis and the main reason for progressive disability in middle-aged and older people. Studies of candidate genes may provide a novel insight and treatment strategy for knee osteoarthritis (KOA). The aim of this study was to investigate the relationship between KOA susceptibility and single-nucleotide polymorphism (SNP) of the ADAMTS-5 gene.Materials and methodsThe case group included 188 patients from Luoyang Orthopedic Hospital with clinically and radiographically diagnosed primary KOA, and the control group included 100 age-matched individuals without KOA. Fifteen ADAMTS-5 SNPs were assayed using MALDI-TOF MS. Allelic and haplotypic frequencies were compared between the groups. The relationship between genotype distribution and risk of KOA was analyzed by multivariate logistic regression.ResultsThe frequency of A allele in rs2249350 site in the KOA group was significantly lower (odds ratio [OR]: 0.761; 95% confidence interval [95% CI]: 0.612–0.947; P = 0.016), while that of C allele was higher than that in the control group (OR: 1.176; 95% CI: 1.025–1.351; P = 0.016). AA genotype and gene model, especially recessive gene model at rs2249350 locus, negatively correlated with KOA risk after adjustment for sex, body mass index, age, and occupation (AA vs. CC: OR: 0.288; 95% CI: 0.124–0.669; P = 0.004; AA vs. CA + CC: OR: 0.348; 95% CI: 0.162–0.749; P = 0.007). Meanwhile, one protective haplotype, GA (rs229054, rs2249350) (OR: 0.763; 95% CI: 0.614–0.949; P = 0.017), and one high-risk haplotype, GC (rs229054, rs2249350) (OR: 1.259; 95% CI: 1.032–1.537; P = 0.019), were found in this study.ConclusionDespite a limited sample size, our study suggests that the rs2249350 polymorphism in the ADAMTS-5 gene is one of the genetic factors influencing the risk of KOA. The A allele and AA genotype of rs2249350 may protect from KOA, whereas C allele and CC genotype increase the risk of KOA. In addition, the GA haplotype (rs229054, rs2249350) might be associated with a decreased risk of KOA, whereas the GC haplotype (rs229054, rs2249350) may be a risk factor for KOA. Additional larger-sized studies in more ethnically diverse populations are needed to confirm these findings.

Association of VEGF+936 C/T Polymorphism with Susceptibility to Type 2 Diabetic Retinopathy: A Meta-Analysis.

The objective of this study is to explore the relationship between the vascular endothelial growth factor (VEGF)+936 C/T polymorphism and the risk of type 2 diabetic retinopathy (T2DR) by a method of meta-analysis. Six online databases were queried to identify studies investigating the VEGF+936 C/T polymorphism that influenced T2DR up to August 2023. The statistical tool of the pooled data was adopted using Stata 15.0 software. The experimental group comprised patients with T2DR, while patients with type 2 diabetes mellitus without retinopathy were considered as the controls. The odds ratio (OR) was utilized as effect size. Eight eligible publications were identified in this review, including 1546 patients with T2DR. The combined results revealed that the VEGF+936 C/T polymorphism was significantly associated with the T2DR risk under the allelic (C/T: OR=0.54, p<0.001), the dominant (CC+CT/TT: OR=0.37, p<0.001), recessive (CC/CT+TT: OR=0.52, p=0.001), homozygous (CC/TT: OR=0.31, p<0.001), and heterozygous (CT/TT: OR=0.55, p=0.005) gene models. No significant correlation was observed regarding the VEGF+936 C/T polymorphism that contributed to the risk of proliferative diabetic retinopathy (PDR) versus non-PDR. In conclusion, the VEGF+936 C/T polymorphism significantly contributed to the T2DR risk. Specifically, at the VEGF+936 C/T locus, the presence of allele C and genotypes CC, CT, and CC+CT were found to be associated with a reduced risk of T2DR.

Association between AGTR1 (c.1166 A>C) Polymorphisms and Kidney Injury in Hypertension.

High blood pressure is the main cause of cardiovascular diseases. Kidney damage is one of the most common organ secondary damage to hypertension. The study of hypertension gene polymorphisms is an important means of precision treatment of primary hypertension. The objective of this study was to explore the relationship between AGTR1 (c.1166 A>C) gene polymorphisms and hypertension combined with kidney damage, while exploring the relationship between codominant, dominant and recessive gene model and hypertension with kidney injury and the susceptibility of different genotypes to hypertension with kidney injury. The distribution of AGTR1 polymorphism in the AGTR1 in hypertensive patients (hypertension group, 292 patients) and hypertension with kidney injury patients (44 patients) were detected and compared by PCR-melting curve method. The genotype distribution of hypertension and combined groups met Hardy-Weinberg equilibrium (p > 0.05); the distribution difference between the three genotypes was statistically significant (p < 0.05), the codominant, dominant and recessive distribution frequency of genotypes (p < 0.05), and no difference between A allele and C allele (p > 0.05). Our study identified the relationship of AGTRA (c.1166 A>C) with hypertension combined with renal injury, and compared the susceptibility of different genetic models, which may provide novel targets for precision gene therapy of hypertension. URL: https://www.chictr.org.cn/indexEN.html; Unique identifier: ChiCTR2100051472.

The effect of AT1R-1166A/C and AT2R-1675A/G polymorphisms on susceptibility to preeclampsia: A systematic review and meta-analysis.

The aim of this meta-analysis is to investigate the association between Angiotensin II type 1 receptor (AT1R)-1166A/C, Angiotensin II type 2 receptor (AT2R)-1675A/G polymorphisms and susceptibility to preeclampsia (PE). Online databases, including Web of Science, PubMed, EMBASE, CINAHL, CENTRAL, Scopus, Lilacs/SciELO, and Chinese National Knowledge Infrastructure, China Wan Fang, China Science and Technology Journal Database, were used to perform the literature search up to April 2022. The odds ratio (OR) and 95% confidence interval (CI) were used as effect size. The data was analyzed by Stata 15.0 software. According to the inclusion and exclusion criteria, a total of 22 case-control studies were identified, including 3524 cases and 6308 controls. Our meta-analysis showed that the AT1R -1166 A/C allele was significantly associated with susceptibility to PE (A vs C: OR = 0.82, 95% CI: 0.69-0.96, P = .013), and there was significant difference in recessive gene model (AA vs AC + CC: OR = 0.81, 95% CI: 0.67-0.97, P = .021). However, no association was found between AT2R-1675A/G polymorphism and susceptibility to PE. our meta-analysis suggested that AT1R-1166A/C polymorphism had an association with susceptibility to PE, but AT2R-1675A/G polymorphism had no association with susceptibility to PE.

A Major Recessive Gene Associated with Anthracnose (Colletotrichum capsici) Resistance in Chilli Pepper

Chilli anthracnose caused by Colletotrichum sp., is an important disease in Bangladesh and many other Asian countries. Recently the local Bangladeshi genotype ‘Comilla-2’ was found resistant to C. capsici. Inheritance of resistant to C. capsici was analyzed in segregating populations derived from a cross of ‘BARI chilli-1’ x ‘Comilla-2’. BARI chilli-1 as susceptible and Comilla-2 as resistant parent was used in the study. Detached matured green fruits were inoculated using the microinjection method. Disease response was evaluated using disease incidence and over all lesion diameter at 8 days after inoculation. The disease reaction of F1 plants in case of disease incidence and overall lesion diameter were clearly skewed to the susceptible parent, with average values of 46.70% and 13.2 mm, respectively. The distribution of disease incidence in the F2 population was skewed toward the susceptible parent and the distribution of overall lesion diameter in the F2 population showed a similar trend. Based on the scale of resistance and susceptibility, less than 25.0% disease incidence or less than 9.0 mm overall lesion diameter were evaluated as resistance. In the cross ‘BARI chilli-1’ x ‘Comilla-2’, the segregation ratios of resistance and susceptibility scored by disease incidence and overall lesion diameter in the F2 , BCr and BCs populations and chi-squared test significantly fitted one recessive gene model i.e. 1:3 Mendelian model. The result indicates that the resistance of ‘Comilla-2’ to C. capsici is controlled by a single recessive gene.

Epithelial nitric oxide synthases (eNOS) 894 G &lt; T polymorphism and diabetic nephropathy susceptibility: A meta-analysis

Abstract Objective To investigate the epithelial nitric oxide synthases (eNOS) 894 G &lt; T polymorphism and diabetic nephropathy (DN) susceptibility by pooling the open published data. Methods Studies relevant to eNOS 894 G &lt; T polymorphism and DN susceptibility published in PubMed, EMBASE, Medline, CNKI, and Wanfang databases were systematically screened by using the text words of endothelial nitric oxide synthase, eNOS, NOS-3, G894T, rs179983, polymorphism, diabetic nephropathy, and DN. The correlation between eNOS 894 G &lt; T polymorphism and DN susceptibility was demonstrated by odds ratio (OR) and corresponding 95% confidence interval (95% CI). The data were combined through fixed or random effect model according to statistical heterogeneity. The publication bias was assessed by Begg’s funnel plot and Egger’s line regression test. Results Twenty-six case-control studies relevant to eNOS 894 G &lt; T polymorphism and DN susceptibility were identified by electronic searching of the related databases. Type 2 diabetes mellitus (T2MD) patients with T allele had increased susceptibility to DN compared with G allele under homologous gene model (TT vs GG) (OR = 1.40, 95% CI: 1.16–1.69, p = 0.001), dominant gene model (TT + GT) vs GG (OR = 1.61, 95% CI: 1.30–2.00, p = 0.000) and recessive gene model TT vs (GT + GG) (OR = 1.39, 95% CI: 1.16–1.66, p = 0.000). Publication bias was not statistically significant for homologous and recessive gene model. Conclusion Based on the present evidence, DN risk was increased in T2MD cases with T allele compared to G allele.

Circulating Inflammatory Mediators and Genetic Polymorphisms of Inflammation Mediators and Their Association with Factors Related to Abdominal Aortic Aneurysm: A Systemic Review and Meta-Analysis.

This study aimed to explore the levels of circulating inflammatory factors CRP, IL-6, IL-10 and TNF- based on the literature review. This study also examined the influence of single nucleotide polymorphism (SNP) sites on the susceptibility of abdominal aortic aneurysm (AAA) using meta-analysis and intended to provide additional information on pathogenesis of AAA research. Electronic databases including PubMed and Web of Science were systemically searched to collect the information on AAA, inflammatory factors such as CRP, IL-6, IL-10, TNF- and the SNP sites for data extraction. Altogether six SNPs in four genes (rs3091244, CRP; rs1800947, CRP; rs1205, CRP; rs1800795, IL-6; rs1800896, IL-10; and rs1800629, TNF) were assessed. This study enrolled altogether 41 relevant investigations involving 9,007 AAA patients to carry out meta-analysis. According to pooled analysis, circulating CRP and IL-6 levels were shown to be related to the AAA, while plasma IL-10 and TNF- levels were not associated with AAA. The circulating CRP level standard mean difference (SMD) was 0.30 (95% confidence interval (CI): 0.17-0.43), the IL-6 level SMD was 0.34 (95% CI: 0.20-0.49), the IL-10 level SMD was -0.01 (95% CI: -0.09-0.06), and the TNF- level SMD was 0.09 (95% CI: 0.00-0.19). Similarly, the odds ratio (OR) of rs3091244 (CRP) under the recessive gene model was 1.70 (95% CI: 1.13-2.57). In addition, individuals with A and T mutant genes at locus rs3091244 might have a higher tendency of AAA susceptibility than those with C allele. Consecutively, the OR was 0.91 (95% CI: 0.51-0.97) for rs1800795 (IL-6) locus in the allele model, and individuals with G mutant gene at locus rs1800795 (IL-6) might be less susceptible to AAA than those with C allele. Meanwhile, the rs1800896 (IL-10) locus had a positive association under the five statistical models, and individuals with A mutant gene at locus rs1800896 might have a higher susceptibility to AAA than those with G allele. Nevertheless, the rs1800947 (CRP), rs1205 (CRP), and rs1800629 (TNF) loci did not have positive correlation under the five statistical models, with no statistical significance. The results indicate that the gene polymorphisms at rs1800629, rs1800947, and rs1205 loci were not related to the AAA susceptibility. Gene polymorphisms in certain known inflammatory mediators related to AAA susceptibility might serve as potential predictive biomarkers for clinical applications. Moreover, SNP of inflammatory mediators relevant to abdominal aortic aneurysmal formation and progression need extensive investigations to confirm these results.

A Sequence Variation in GmBADH2 Enhances Soybean Aroma and Is a Functional Marker for Improving Soybean Flavor.

The vegetable soybean (Glycine max L. Merr.) plant is commonly consumed in Southeast Asian countries because of its nutritional value and desirable taste. A “pandan-like” aroma is an important value-added quality trait that is rarely found in commercial vegetable soybean varieties. In this study, three novel aromatic soybean cultivars with a fragrant volatile compound were isolated. We confirmed that the aroma of these cultivars is due to the potent volatile compound 2-acetyl-1-pyrroline (2AP) that was previously identified in soybean. A sequence comparison of GmBADH1/2 (encoding an aminoaldehyde dehydrogenase) between aromatic and non-aromatic soybean varieties revealed a mutation with 10 SNPs and an 11-nucleotide deletion in exon 1 of GmBADH2 in Quxian No. 1 and Xiangdou. Additionally, a 2-bp deletion was detected in exon 10 of GmBADH2 in ZK1754. The mutations resulted in a frame shift and the introduction of premature stop codons. Moreover, genetic analyses indicated that the aromatic trait in these three varieties was inherited according to a single recessive gene model. These results suggested that a mutated GmBADH2 may be responsible for the aroma of these three aromatic soybean cultivars. The expression and function of GmBADH2 in aromatic soybean seeds were confirmed by qRT-PCR and CRISPR/Cas9. A functional marker developed on the basis of the mutated GmBADH2 sequence in Quxian No. 1 and Xiangdou was validated in an F2 population. A perfect association between the marker genotypes and aroma phenotypes implied that GmBADH2 is a major aroma-conferring gene. The results of this study are potentially useful for an in-depth analysis of the molecular basis of 2-AP formation in soybean and the marker-assisted breeding of aromatic vegetable soybean cultivars.

Correlation between methylene tetrahydrofolate reductase (MTHFR) gene rs1801133 C&gt;T polymorphisms and risk of osteoporosis

Abstract Objective To evaluate the correlation between methylene tetrahydrofolate reductase (MTHFR) gene rs1801133 C&gt;T polymorphisms and risk of osteoporosis. Methods We searched the clinical studies related to MTHFR gene rs1801133 C&gt;T polymorphisms and risk of osteoporosis in the electronic databases of PubMed, Web of Science, EMBASE, China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Database (CBM) and included the suitable publications in the present meta-analysis according to the inclusion and exclusion criteria. The data of included studies were extracted and pooled by a random or fixed-effect model. The odds ratio (OR) and 95% confidence interval (95% CI) were applied to demonstrate the correlation between MTHFR gene rs1801133 C&gt;T polymorphisms and the risk of osteoporosis. Publication bias was assessed by Begg’s funnel plot and Egger’s line regression test. Results Seven case–control clinical studies were included and a data combination was made. The data was pooled by the fixed effect model because of no obvious statistical heterogeneity. The pooled results indicated that people with the T allele had increased risk of developing osteoporosis under the homologous gene model (TT vs CC) (OR = 2.36, 95% CI: 1.81–3.08, p &lt; 0.05), dominant gene model (TT + CT) vs CC (OR = 1.47, 95% CI: 1.21–1.77, p &lt; 0.05) and recessive gene model TT vs (CC + CT) (OR = 2.16, 95% CI: 1.71–2.74, p &lt; 0.05). Egger’s line regression test indicated no significant publication bias for the present meta-analysis in the above homologous, dominant, and recessive gene models. Conclusion The MTHFR gene rs1801133 C&gt;T polymorphisms are associated with osteoporosis and subjects with the T allele have an increased risk of developing osteoporosis.

Screening of eggplant genotypes for resistance to bacterial wilt disease caused by Clavibacter michiganensis subsp. michiganensis

Clavibacter michiganensis subsp. michiganensis (Cmm) is one of the phytopathogenic bacteria causing bacterial wilt disease and severe yield losses in tomatoes and other solanaceous vegetables. Although there are some reports on Cmm infections in eggplants (Solanum melongena), there is no information available on the resistance sources and genetic control of the resistance to Cmm in this crop. We performed a search for resistance sources to Cmm in eggplants, in a set of 46 genotypes including landraces, inbred lines and cultivars and some cultivated and wild relatives, as well as an analysis of the genetic control of the resistance. A mixture of different Cmm strains from different genomic groups was used for the screening. Plants were inoculated through the injection of 10 µL of a Cmm suspension at a concentration of 10&lt;sup&gt;7&lt;/sup&gt; cfu/mL in a single point of the stem. The symptoms were recorded at nine weeks after the inoculation with a 0–4 symptoms scale. The differences were observed in the symptoms in the collection evaluated, with the disease severity index of the genotypes ranging from 0.00 to 4.00. While 31 genotypes displayed no symptoms, three cultivated eggplant genotypes were highly susceptible. Reciprocal F1 and F2 generations were obtained from the crosses between the most susceptible genotype (CT30) and a resistant one (CT49). The genetic control of the resistance adjusted well to one dominant and one recessive gene model underlying the resistance to Cmm. These results are important for selection and breeding for resistance to Cmm in eggplants.

Meta-analysis of the association between adiponectin SNP 45, SNP 276, and type 2 diabetes mellitus.

ObjectiveThe present study aimed to determine whether the polymorphisms at rs2241766 and rs1501299 on the ADIPOQ gene were related to the susceptibility of type 2 diabetes mellitus (T2DM).MethodsEight databases, PubMed, GWAS, Embase, Lochrane, Ebsco, CNKI (Chinese National Knowledge Infrastructure), VIP (Viper Database) and ChinaInfo were searched, and a meta-analysis of susceptibility was conducted between SNP45, SNP276 polymorphisms and T2DM. Furthermore, HWE test was conducted to assess the genetic balance of the study, evaluate the quality of Newcastle–Ottawa quality assessment scale (NOS), and establishing allelic, dominant, recessive, heterozygous, and homozygous gene models.ResultsThis meta-analysis included 53 articles, encompassing 9285 cases with rs2241766 and 14156 controls and 7747 cases with rs1501299 and 10607 controls. For the rs2241766 locus, a significant correlation was found in the three models by the subgroup analysis. Western Asians: dominant gene model (TT + TG vs. GG, P = 0.01); heterozygous gene model (TG vs. GG, P = 0.02); homozygous gene model (TT vs. GG, P = 0.01). South Asians: dominant gene model (TT + TG vs. GG, P = 0.004); heterozygous gene model (TG vs. GG, P = 0.009); homozygous gene model (TT vs. GG, P = 0.005). However, no statistically significant correlation was established among the five genetic models for rs1501299 locus.ConclusionThe findings of the present study indicated that the T allele of rs2241766 polymorphism is the susceptibility locus of T2DM in the West Asian population, but has a protective effect in the South Asian population, albeit further studies are needed in other populations. Also, no association was found between the ADIPOQ rs1501299 polymorphism and T2DM.

Significant Associations between AXIN1 rs1805105, rs12921862, rs370681 Haplotypes and Variant Genotypes of AXIN2 rs2240308 with Risk of Congenital Heart Defects.

This study aimed to investigate possible associations of the susceptibility to congenital heart defects (CHDs) with AXIN1 rs1805105, rs12921862 and rs370681 gene variants and haplotypes, and AXIN2 rs2240308 gene variant. Significant associations were identified for AXIN1 rs370681 and AXIN2 rs2240308 variants. AXIN1 rs370681 variant was significantly associated with decreased odds of CHDs (adjusted OR varying from 0.13 to 0.28 in codominant, dominant and recessive gene models), while the AXIN2 rs2240308 variant was associated with increased odds of CHD in the dominant model. The haplotype-based generalized linear model regression of AXIN1 rs1805105, rs12921862 and rs370681 variants revealed that C-C-C and C-C-T haplotypes significantly increased the risk of CHDs (p < 0.05). No significant second order epistatic interactions were found between investigated variants (AXIN1 rs1805105, rs12921862, rs370681, and AXIN2 rs2240308). Our conclusion is that AXIN1 rs1805105, rs12921862, and rs370681 (C-C-C and C-C-T) haplotypes and AXIN2 rs2240308 contribute to CHDs susceptibility.

Association of PNPLA3 rs738409 G/C gene polymorphism with nonalcoholic fatty liver disease in children: a meta-analysis

BackgroundNonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease worldwide. Current studies have shown that PNPLA3 (Patatin-like phospholipase domain containing 3) rs738409 G/C gene polymorphism is associated with adult nonalcoholic fatty liver disease [1, 2].But there is no consensus on the relationship between PNPLA3 rs738409 G/C gene polymorphism and children NAFLD due to differences in population samples. To this end, a meta-analysis of published research is conducted to comprehensively assess the relationship between PNPLA3 gene polymorphism and NAFLD in children.MethodsWe searched MEDLINE, PubMed, EMBASE, and CENTRAL databases from inception to May 2019. Case-control studies assessing the relationship between PNPLA3 rs738409 G/C gene polymorphism with non-alcoholic fatty liver disease in children were selected according to inclusion and exclusion criteria. Random effects model was used to quantify the association between the PNPLA3 rs738409 G/C gene polymorphism and the susceptibility of children’s NAFLD. Fixed effects model was used to quantify the relationship between the PNPLA3 rs738409 G/C gene polymorphism and the severity of NAFLD in children. The Stata 12.0 software was employed for data analysis.ResultsA total of nine case-control studies were included in this meta-analysis containing data of 1173 children with NAFLD and 1792 healthy controls. Five studies compared NAFLD children and non-NAFLD healthy populations. Statistical analysis showed that PNPLA3 gene polymorphism was significantly associated with children’s NAFLD in the allele contrast, dominant, recessive and over dominant models (G vs C,OR = 3.343, 95% CI = 1.524–7.334; GG + GC vs CC,OR = 3.157, 95% CI = 1.446–6.892;GG vs GC + CC,OR = 5.692, 95% CI = 1.941–16.689; GG + CC vs GC,OR = 2.756, 95% CI = 1.729–4.392). Four case-control studies compared Children with nonalcoholic fatty liver (NAFL) and children with nonalcoholic steatohepatitis (NASH). The results showed that the PNPLA3 gene polymorphism was also significantly associated with the severity of NAFLD in children in recessive gene model (GG vs GC + CC,OR = 14.43, 95% CI = 5.985–34.997); The Egger’s test revealed no significant publication bias.ConclusionsMeta-analysis showed that PNPLA3 gene polymorphism was significantly associated with susceptibility and severity of NAFLD in children.

Meta-analysis of angiotensin-converting enzyme insersion/delection polymorphism and pre-eclampsia susceptibility.

In recent years, there were many studies on angiotensin-converting enzyme insersion/delection (ACE I/D) polymorphism and pre-eclampsia susceptibility, but the conclusion was still inconclusive. Our study is to explore the relationship between the ACE I/D polymorphism and the risk of pre-eclampsia. The literature on the relationship between ACE I/D gene polymorphism and Pre-eclampsia susceptibility was obtained by searching the databases of Wanfang, VIP, Medline, CNKI, Embase, Pubmed and Springerlink, which was published from the establishment of the databases to October 2019. Taking the odds ratio (OR) value and its 95% confidence interval (CI) as the effect size, the Meta-analysis was carried out by using stata 15.0 software. Thirty articles, consisting of 3184 patients and 3912 controls, were included. The results showed that allele D was compared with allele I, with the OR value of 1.29 (95% CI: 1.12 ~ 1.50, P < 0.05). Subgroup analysis showed that in Caucasians, allele D was associated with OR of 1.28 (95% CI: 1.08 ~ 1.53, P < 0.05). There was no significant difference in Asians. There was statistical significance in recessive gene model and homozygous gene model, as well as in that of Asian and Caucasian. In homozygous model, there was statistical significance, but subgroup analysis showed there was no statistical significance in Asian and Caucasian. There was no statistical significance in dominant model and heterozygous model. The polymorphism of ACE I/D gene was associated with the risk of pre-eclampsia. Allele D and genotype DD may increase the risk of Pre-eclampsia in pregnant women.

Influence of polymorphisms in VEGF, TNF-α, and GSTP1 genes on retinopathy of prematurity risk: a Meta-analysis

Purpose To investigate the influence of polymorphisms in vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), and glutathione S-transferase Pi isoform (GSTP1) genes on retinopathy of prematurity (ROP) risk, we performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant meta-analysis. Methods An exhaustive search was conducted in PubMed, Web of Science, and CNKI for genetic studies evaluating the relationship between VEGF (−460 T/C, +936 C/T, −634 G/C, and −2578 C/A), TNF-α (−308 G/A) and GSTP1 (Ile/Val) polymorphisms and ROP risk from inception until November 2019. Odds ratio (OR) with the 95% confidence interval (CI) were used for estimating combined effect size. The quality of the included studies was evaluated using the Newcastle-Ottawa Scale (NOS). Results A total of 14 studies met the inclusion criteria. The meta-analyses revealed that VEGF − 460 T/C was associated with ROP risk in the allele model (C vs. T, OR = 0.83, 95% CI: 0.74–0.94, POR=0.004), homozygous gene model (CC vs. TT, OR = 0.70, 95% CI: 0.54–0.91, POR=0.008), dominant gene model (CC + TC vs. TT, OR = 0.80, 95% CI: 0.67–0.95, POR = 0.012), and recessive gene model (CC vs. TC + TT, OR = 0.74, 95% CI: 0.59–0.94, POR = 0.014). However, we did not find significant differences in the genotype and allele distribution of VEGF + 936 C/T, −634 G/C, −2578 C/A, TNF-α − 308 G/A and GSTP1 Ile/Val polymorphisms, between ROP and control group (p > .05). Conclusions VEGF polymorphism −460 T/C was associated with a lower ROP risk. Further research is warranted to investigate haplotype effects of VEGF polymorphisms on the risk of ROP.

Association between polymorphisms of epidermal growth factor 61 and susceptibility of lung cancer: A meta-analysis.

To explore the association between epidermal growth factor (EGF) 61A/G polymorphism and lung cancer.All eligible case-control studies published up to August, 2019 were identified by searching PubMed, The excerpta medica database, China Academic Journals Full-text Database, China Biology Medicine, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang databases. Two researchers independently identified the literature, extracted data, and evaluated quality according to inclusion and exclusion criteria. Meta-analysis was performed by Stata 15.0.A total of 6 studies is included, including 1487 cases and 2044 control subjects. Compared with allele A, allele G was considered to have no association with the risk of lung cancer, odds ratio = 1.07 (95% confidence interval: 0.98–1.15). GG recessive genotype, GG + GA dominant genotype, GG homozygote genotype and GA heterozygote genotype were found out that all of them are not associated with the risk of lung cancer. No association between EGF 61A/G polymorphism and lung cancer was found out by ethnical subgroup analysis. However, in view of the limitations of this study, such as the results of quantitative and sensitivity analysis may be lack of accuracy, so the conclusions of allele model and recessive gene model should be made carefully.It suggested that there was no association between polymorphism of EGF 61A/G and susceptibility of lung cancer.

Interleukin-6 polymorphisms in HCC patients chronically infected with HCV

Hepatocellular carcinoma is a primary liver malignancy in which the risk of development is always multifunctional. Interleukin-6 is a proinflammatory and multifunctional cytokine, which plays an important role in the immune response, haematopoiesis and defence against viral infection. We aimed to evaluate the frequency of Interleukin-6 mutations (rs2069837 and rs17147230) associated with genetic risk of hepatocellular carcinoma in Khyber Pakthunkhwa population. A total of 72 hepatocellular carcinoma cases and 38 controls were included in this study. The genomic DNA was extracted from the peripheral blood cells and Interleukin-6 genotyping was performed using T-ARMS-PCR technique. Our results show a significant increase risk of developing hepatocellular carcinoma with the mutation within Interleukin-6 gene with heterozygous G allele (rs2069837) (OR = 10.667, 95%CI = 3.923–29.001, p = < 0.0001) and heterozygous T allele (rs17147230) (OR = 75.385, 95%CI = 9.797–580.065, p = < 0.0001). However, under recessive gene model the results were insignificant in case of Interleukin-6 rs2069837 (OR = 0.605, 95%CI = 0.217–1.689, p = 0.337), while significant in case of Interleukin-6 rs17147230 (OR = 0.298, 95%CI = 0.121–0.734, p = 0.0085). In conclusion, Interleukin-6 mutation is associated with hepatocellular carcinoma susceptibility. More related studies with other associated interleukins and their whole gene sequencing will be required.

MTHFR-C677T Gene Polymorphism and Susceptibility to Acute Lymphoblastic Leukemia in Children: A Meta-Analysis.

The association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism (rs1801133) and childhood acute lymphoblastic leukemia (ALL) is inconsistent. To explore the relationship between MTHFR-C677T polymorphism and susceptibility to childhood ALL. PubMed, EMBASE, Web of Science, CNKI, Wanfang, VIP, and other databases were searched from the establishment of the database to November 2019, and all the case-control studies that met the inclusion criteria were collected. Stata 15.0 was used for meta-analysis, with calculation of the odds ratio (OR) of the relationship between MTHFR-C677T polymorphism and childhood ALL susceptibility. Ethnicity was analyzed by subgroup analysis. A total of 26 studies were included in this meta-analysis, including 4,682 children with ALL and 7144 controls. The results showed that there was no significant difference in the comparison of population of allele model, dominant gene model, recessive gene model, homozygous gene model, heterozygous gene model, and the comparison of Caucasian children. The results of the Asian child analysis suggested that the combined OR of the dominant gene model (CC + CT versus TT), homozygous model (CC versus TT) and heterozygous model (CT versus TT) was 1.32 (95% confidence interval [CI]: 1.03-1.70), 1.37 (95% CI: 1.02-1.84), and 1.27 (95% CI: 1.01-1.59), respectively, with statistically significant differences. However, there was no significant difference between the allele model and recessive gene model among Asian children. The MTHFR C677T polymorphism is related to ALL in children, especially in Asian children. CC + CT, CC, and CT genotypes can increase the risk of ALL, but no association has been found in Caucasian children.

Relationship between polymorphisms in -572G/C interleukin 6 promoter gene polymorphisms (rs1800796) and risk of rheumatoid arthritis: A meta-analysis.

This meta-analysis was aimed to investigate the association between -572G/C interleukin (IL)-6 gene polymorphism and occurrence risk of rheumatoid arthritis (RA). Literature search was conducted in PubMed, Embase, Springer and Google Scholar up to November 2018. The pooled odds ratios (ORs) and 95% confidence interval (CI) were calculated by Revman 5.3. A total of six case-control studies were included in this meta-analysis. In the allele model (G vs C), homozygous gene model (GG vs CC), recessive gene model (GG vs GC+CC), and dominant gene model (GG+GC vs CC), the pooled estimate indicated there was significant association between -572G/C IL-6 gene polymorphism and risk of RA. However, no significant statistical results were found in meta-analyses of heterozygote gene models. The -572G/C IL-6 gene polymorphism is associated with the risk of RA. The GG genotype may be the main contributor in increasing susceptibility to RA.