Allele Model Research Articles

Polymorphism rs143384 GDF5 reduces the risk of knee osteoarthritis development in obese individuals and increases the disease risk in non-obese population

BackgroundWe investigated the effect of obesity on the association of genome-wide associative studies (GWAS)-significant genes with the risk of knee osteoarthritis (KOA).MethodsAll study participants (n = 1,100) were divided into 2 groups in terms of body mass index (BMI): BMI ≥ 30 (255 KOA patients and 167 controls) and BMI < 30 (245 KOA and 433 controls). The eight GWAS-significant KOA single nucleotide polymorphisms (SNP) of six candidate genes, such as LYPLAL1 (rs2820436, rs2820443), SBNO1 (rs1060105, rs56116847), WWP2 (rs34195470), NFAT5 (rs6499244), TGFA (rs3771501), GDF5 (rs143384), were genotyped. Logistic regression analysis (gPLINK online program) was used for SNPs associations study with the risk of developing KOA into 2 groups (BMI ≥ 30 and BMI < 30) separately. The functional effects of KOA risk loci were evaluated using in silico bioinformatic analysis.ResultsMultidirectional relationships of the rs143384 GDF5 with KOA in BMI-different groups were found: This SNP was KOA protective locus among individuals with BMI ≥ 30 (OR 0.41 [95%CI 0.20–0.94] recessive model) and was disorder risk locus among individuals with BMI < 30 (OR 1.32 [95%CI 1.05–1.65] allele model, OR 1.44 [95%CI 1.10–1.86] additive model, OR 1.67 [95%CI 1.10–2.52] dominant model). Polymorphism rs143384 GDF5 manifested its regulatory effects in relation to nine genes (GDF5, CPNE1, EDEM2, ERGIC3, GDF5OS, PROCR, RBM39, RPL36P4, UQCC1) in adipose tissue, which were involved in the regulation of pathways of apoptosis of striated muscle cells.ConclusionsIn summary, the effect of obesity on the association of the rs143384 GDF5 with KOA was shown: the “protective” value of this polymorphism in the BMI ≥ 30 group and the “risk” meaning in BMI < 30 cohort.

Association of TIMP2 418 G/C and MMP Gene Polymorphism with Risk of Urinary Cancers: Systematic Review and Meta-analysis.

Aim: The matrix metalloproteinases (MMPs) inhibit tissue inhibitors of metalloproteinases (TIMPs), playing a notable role in various biological processes, and mutations in TIMP2 genes impact a variety of urinary cancers. In this study, we analyze and evaluate the potential involvement of the TIMP2 418 G/C and MMP gene polymorphism in the etiology of urinary cancer. Methodology: For suitable case-control studies, a literature search was undertaken from various database sources such as PubMed, EMBASE, and Google Scholar. Incorporated into the analysis were case-control or cohort studies that documented the correlation between TIMP2 418 G/C and urological cancers. MetaGenyo served as the tool for conducting the meta-analysis, employing a fixed-effects model. The collective odds ratios, along with their corresponding 95% confidence intervals, were calculated and presented to assess the robustness of the observed associations. Results: A total of seven studies involving controls and cases out of recorded 1265 controls and 1154 cases were analyzed to ascertain the significant association of the TIMP2 gene with urologic cancer. No statistically significant correlation was observed between allelic, recessive, dominant, and overdominant models for the genetic variant under investigation. A 95% confidence interval (CI) and odds ratio (OR) were computed for each model, considering p-values <0.05. The OR and 95% CI for the allelic model were 0.99 and 0.77-1.27, respectively, whereas the respective values were 1.00 and 0.76-1.32 for the recessive model. In the dominant contrast model, OR and 95% CI were 1.09 and 0.62-1.90, while the same were 0.93 and 0.77-1.12 for the overdominant model. A funnel plot was used to reanalyze and detect the results as statically satisfactory. Conclusions: As a result of the data obtained, the TIMP2 gene polymorphism does not correlate statistically with cancer risk. The significance of this finding can only be confirmed using a large population, extensive epidemiological research, a comprehensive survey, and a better understanding of the molecular pathways associated.

The association between genetic polymorphisms of matrix metalloproteinases and knee osteoarthritis: A systematic review and meta-analysis.

To investigate the linkage of matrix metalloproteinase (MMP) gene polymorphisms with the pathogenesis of knee osteoarthritis (OA). This meta-analysis study systematically retrieved relevant studies from PubMed, Embase, the Cochrane Central, Wanfang Data, CNKI, and SinoMed up to November 2020. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the association between MMP gene polymorphisms and OA. A total of nine case-control studies comprising 1719 knee OA patients and 1904 controls were included in this meta-analysis. The results revealed that MMP-1-1607 (rs1799750) 1G/2G polymorphism was not significantly associated with knee OA risk in four genetic models (OR (95% CI): allele model: 0.89 (0.57, 1.40), p = .615); dominant mode: 0.82 (0.47, 1.44), p = .486; recessive model: 0.88 (0.49, 1.57), p = .659; homozygote model: 0.79 (0.34, 1.82), p = .576. The association was significant for dominant model of MMP-3 C/T: 1.54 (1.10-2.15), p = .013, especially in Asian ethnicity (1.63 (1.11, 2.39), p = .013). Variants of MMP-13 C/T polymorphism were associated with increased risk of knee OA development based on dominant model: 1.56 (1.19, 2.06), p = .001 and homozygote model: 2.12 (1.44, 3.13), p < .001, and there were significant associations between MMP-13 C/T polymorphism and knee OA risk in Asian ethnicity under different genetic models (all p > .05). Present evidence suggested that the gene polymorphisms of MMP-1-1607 1G/2G may not be associated with the risk of OA. But, the dominant model of MMP-3 and MMP-13 polymorphisms in Asian ethnicity was significantly correlated with knee OA.

Role of polymorphism in vitamin D receptor gene on diabetic foot ulcer: A systematic review and meta-analysis

Context: Once vitamin D is converted to its active form, the molecule binds to its receptor (VDR) and performs its function as a transcription factor in modulating immune response, inflammation cascade, and insulin signaling. Among diabetic individuals, these activities are thought to be correlated with foot ulceration. Gene polymorphisms could change the function of VDR, thereby affecting the development of foot ulceration among individuals with diabetes. Aims: To construct evidence on the role of VDR gene variants or single nucleotide polymorphisms (SNPs) on diabetic foot ulcers. Methods: Records reporting the distribution of genotypes and/or alleles among diabetic foot ulcer (DFU) patients and published until 10 March 2023 were retrieved from 12 major databases using predetermined keywords. The original research articles included in the study were assessed for reporting quality using the Newcastle Ottawa Scale. The quality of genotypic and allelic data was appraised by Hardy-Weinberg equilibrium (HWE). A quantitative analysis-based fixed-effects model was performed to estimate the proportion of genotype and allele frequencies among DFU patients. Results: Three studies were included in the systematic review reporting the FokI (rs2228570), TaqI (rs731236), BsmI (rs1544410), and ApaI (rs7975232) SNPs. Based on pooled estimates, among DFU patients CC, CT, and TT genotypes of VDR FokI SNPs had a prevalence of 45%, 43%, and 12%, respectively, without significant heterogeneity found in the reported data (p-Het&lt;0.001; I2&gt;0%). ApaI and FokI were associated with DFU, while no association in all genotypic and allelic models was found between TaqI or BsmI and DFU. CC genotype of BsmI and T allele of FokI was associated with oxidative stress (one of the underlying factors in DFU). Conclusions: Certain genotypes and alleles of FokI and ApaI SNPs could act as the risk factor for foot ulceration among diabetic individuals. More high-quality studies are still needed to draw solid conclusions on the role of VDR SNPs among DFU patients.

Associations of toll-like receptor polymorphisms with systemic lupus erythematosus: A meta-analysis

ObjectiveThe objective of this study was to examine whether polymorphisms in toll-like receptors 7 and 4 (TLR7 and 4) contribute to vulnerability to systemic lupus erythematosus (SLE). MethodsWe searched MEDLINE, Embase, and Web of Science for relevant articles and performed a meta-analysis to investigate the relationship between TLR7 rs179008, rs3853839, rs1790010, TLR4 rs4986791, and rs798690 polymorphisms and SLE. ResultsEighteen studies and 16 papers including 8022 patients with SLE and 9822 healthy controls were retrieved. Meta-analysis revealed that the TLR7 rs179008 T variant was not associated with SLE (OR = 1.008, 95% CI = 0.849–1.394, P = 0.504). Ethnic classification revealed no association between the TLR7 rs179008 T gene and SLE in either European or Latin American groups. Additionally, homozygous comparison, recessive, and dominant models revealed no association between the TLR7 rs179008 variant and SLE. In contrast, a significant association between SLE and the TLR7 rsrs3853839 GG + GA allele (OR = 2.135, 95% CI = 1.502–3.035, <0.001; OR = 23.20, 95% CI = 14.13–38.08, <0.001) was observed in the Arab and Asian groups. The T variant of TLR7 rsrs179010 was also associated with SLE in Asians (OR = 1.177, 95% CI = 1.048–1.321, P = 0.006). In contrast, the TLR4 rs4986791 variant was not associated with SLE in Europeans when allele, homozygous comparison, recessive, and dominant models were used. Furthermore, no association between the TLR4 rs4986790 variant and SLE risk in Europeans was found using any genomic model. ConclusionsMeta-analysis revealed that the TLR7 rs3853839 variant is associated with SLE risk in Asians and Arabs and that TLR7 rs179010 is associated with SLE in Asians. However, TLR7 rs179008, TLR4 rs4986791, and TLR rs798690 polymorphisms were not associated with SLE risk.

Association between Vitamin D Receptor Polymorphism and Susceptibility to Oral Lichen Planus and Oral Squamous Cell Carcinoma.

Oral squamous cell carcinomas (OSCC) comprise 90-95% of oral cancers. Early diagnosis improved the survival rate of OSCC patients to 80-90%. Oral lichen planus (OLP) is a chorionic inflammatory disease with malignancy potential. The vitamin D receptor (VDR) plays a critical role in the pathogenesis of oral cancer. This study aimed to determine the association between VDR rs7975232 (Apa I) polymorphism and potential susceptibility to OLP and OSCC risks. In this prospective case-control study, a total of 120 blood samples were obtained from OSCC patients (n=29), OLP (n=50), and controls (n=40). VDR rs7975232 polymorphism was studied using the Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) method. Statistical analysis was performed with SPSS Version 23 software. Data were expressed as means ± standard deviation (SD). Age, sex, allelic frequency, and genotyping were compared using the chi-square test. A p-value of less than 0.05 was regarded as statistically significant. The disease risk was estimated by Odds ratio (OR) with a 95% confidence interval. A significant age difference was observed between the controls and the OSCC group (p=0.001). A significant difference was observed in Aa and aa genotypes compared with AA between OSCCs and controls. Moreover, dominant (p<0.001), additive (p<0.001), and allelic (p=0.001) models were different between groups. There was a positive association between rs7975232 VDR polymorphism and susceptibility to OSCC. More experimental evidence must reveal the possible association between rs7975232 and the risk of OLP in a larger cohort.

Association between vitamin D receptor gene polymorphisms and genetic susceptibility to benign prostatic hyperplasia: A systematic review and meta-analysis.

Benign prostatic hyperplasia (BPH) is one of the global public health challenges due to the complexity of its mechanisms of occurrence. Many studies have suggested that vitamin D receptor gene polymorphisms are associated with BPH susceptibility. Still, their conflicting findings need to be analyzed in aggregate to gain a better understanding. We identified 10 trials involving 1539 BPH cases and 1915 controls through a systematic search of Embase using, data obtained from the Web of Science, PubMed, and China Knowledge Network databases as of December 31, 2021. A meta-analysis was performed to investigate the association between 4 constant polymorphisms of this associated vitamin D receptor gene (Fok-1, Bsm-1, Taq-1, and Apa-1) and BPH risk. In the overall population analysis, a significant positive association with BPH risk was found only in the Taq-1 variant (P < .001). Of these, the pure-hybrid model (95% confidence interval [CI] = 1.384-3.196), the heterozygous model (95% CI = 1.207-2.021), the dominant model (95% CI = 1.312-2.133) and the allelic inheritance model (95% CI = 1.205-1.730) showed low heterogeneity. In subtype analyses, Bsm-1 variants showed a significant association with BPH risk for both the recessive (95% CI = 0.100-0.943, P = .039) and over-dominant (95% CI = 1.553-3.100, P = 0) models in the Caucasian population, and for the recessive (95% CI = 1.242-3.283, P = .039) and over-dominant (95% CI = 0.281-0.680, P = 0) models in the Asian population. In addition, a high degree of heterogeneity was found in the subgroup analysis of the association between Fok-1 variants and BPH risk. Overall, there is an association between vitamin D receptor polymorphisms and BPH risk. Identification of BPH susceptibility by vitamin D receptor gene polymorphisms has potential.

Impact of the MIF -173G/C variant on cardiovascular disease risk: a meta-analysis of 9,047 participants.

Many factors contribute to the risk of cardiovascular disease (CVD), an umbrella term for several different heart diseases, including inflammation. Macrophage migration inhibitory factor (MIF) is an important immune modulator that has been shown to be involved in the pathogenesis of different heart diseases, so understanding pathogenic variants of the MIF gene is important for risk stratification. We therefore conducted a meta-analysis to investigate whether the MIF -173G/C (rs755622) polymorphism is associated with CVD. The PubMed, Science Direct, and Embase databases were searched from inception to June 2023 for case-control studies of the MIF -173G/C polymorphism and its relationship to any type of CVD. Correlations between the MIF -173G/C polymorphism and CVD were estimated by pooling the odds ratios (ORs) with 95% confidence intervals in allelic, dominant, and recessive models using random-effects meta-analysis. A total of 9,047 participants (4141 CVD cases and 4906 healthy controls) from 11 relevant studies were included. In the total population, there was no significant association between the MIF -173G/C (rs755622) polymorphism and the risk of developing CVD in the three different models. In a stratified analysis by ethnicity, the allelic model (C vs G) was significantly associated with CVD in the Arab and Asian populations (OR = 0.56, CI 0.42 -0.75 and OR = 1.28, CI 1.12 -1.46, respectively); the dominant model (CC+CG vs GG) was significantly associated with CVD in the Arab population (OR = 0.42, CI 0.30 -0.61); while the recessive model (GG+GC vs CC) was associated with CVD susceptibility in the Arab population (OR = 3.84, CI 1.57 -9.41). There were no significant associations between the MIF -173 G/C polymorphism and CVD risk in the European population. Conclusion, the MIF -173G/C polymorphism is associated with CVD in some populations. https://www.crd.york.ac.uk/PROSPERO/, PROSPERO (CRD42023441139).

Association between CCL5, CCL11, and CCL17 polymorphisms and atopic dermatitis risk: A systematic review and meta-analysis.

Atopic dermatitis (AD) is a common and recurrent inflammatory disease with strong genetic susceptibility. The abnormal production of chemokines plays an important role in the occurrence and development of AD. A comprehensive online literature search was performed in databases of China National Knowledge Infrastructure, Wanfang, VIP China Science and Technology Journal Database, China Biomedical Literature Database, PubMed, Embase and Cochrane Library to retrieve relevant articles published from January 2000 to October 2022. The odds ratio (OR) with its 95% confidence interval (CI) was employed to calculate this relationship. A total of 7 studies were finally screened out, including 1316 AD patients and 1099 controls. There were 3 studies for CC chemokine ligand 5 (CCL5) polymorphisms, 2 for CCL11 polymorphisms, and 2 for CCL17 polymorphisms, respectively. The meta-analysis revealed a significant association between the CCL5 - 403G/A polymorphism and AD under the allelic model (A vs G: OR = 1.25, 95% CI = 1.02-1.52, P = .03), heterozygous model (AG vs GG: OR = 1.40, 95% CI = 1.08-1.80, P = .01) and dominant model (AA + AG vs GG: OR = 1.38, 95% CI = 1.08-1.76, P = .01) in a fixed-effect model. The allelic model (G vs C: OR = 1.46, 95% CI = 1.07-1.98, P < .01) and dominant model (GG + GC vs CC: OR = 1.74, 95% CI = 1.23-2.47, P < .001) of the CCL5 - 28C/G polymorphism were also associated with an increased risk of AD. However, this significant association was not found in other alleles and genotypes (P > .05). Our results show that the A allele, AG and AA + AG genotypes of the CCL5 - 403G/A polymorphism, the G allele and GG + GC genotype of the CCL5 - 28C/G polymorphism are risk factors for AD. Future studies with large population are still needed to further explore those correlations.

Associative role of HLA-DRB1 as a protective factor for susceptibility and progression of Parkinson's disease: a Chinese cross-sectional and longitudinal study.

Previous genome-wide association studies investigating the relationship between the HLA-DRB1 and the risk of Parkinson's disease (PD) have shown limited racial diversity and have not explored clinical heterogeneity extensively. The study consisted of three parts: a case-control study, a cross-sectional study, and a longitudinal cohort study. The case-control study included 477 PD patients and 477 healthy controls to explore the relationship between rs660895 and PD susceptibility. The cross-sectional study utilized baseline data from 429 PD patients to examine the correlation between rs660895 and PD features. The longitudinal study included 388 PD patients who completed a 3-year follow-up to investigate the effects of rs660895 on PD progression. In the case-control study, HLA-DRB1 rs660895-G allele was associated with a decreased risk of PD in allele model (adjusted OR=0.72, p = 0.003) and dominant model (AG + GG vs. AA: adjusted OR = 0.67, p = 0.003). In the cross-sectional analysis, there was no association between rs660895 and the onset age, motor phenotype, or initial motor symptoms. In the longitudinal analysis, PD patients with the G allele exhibited a slower progression of motor symptoms (MDS-UPDRS-III total score: β = -5.42, p < 0.001, interaction ptime × genotype < 0.001) and non-motor symptoms (NMSS score: β = -4.78, p = 0.030, interaction ptime × genotype < 0.001). Our findings support HLA-DRB1 rs660895-G allele is a protective genetic factor for PD risk in Chinese population. Furthermore, we also provide new evidence for the protective effect of rs660895-G allele in PD progression.

Association between DPP6 gene rs10260404 polymorphism and increased risk of sporadic amyotrophic lateral sclerosis (sALS): a meta-analysis.

Sporadic amyotrophic lateral sclerosis (sALS) is a severe neurodegenerative disease characterized by continuous diminution of motor neurons in the brain and spinal cord. Earlier studies indicated that the DPP6 gene variant has a role in the development of sALS. This meta-analysis was designed to uncover the role of rs10260404 polymorphism of the DPP6 gene and its association with sALS. All case-control articles published prior to October 2022 on the association between DPP6 (rs10260404) polymorphism and sALS risk were systematically extracted from different databases which include PubMed, PubMed Central, and Google Scholar. Overall odds ratios (ORs) and "95% confidence intervals (CIs)" were summarized for various genetic models. Subgroup and heterogeneity assessments were performed. Egger's and "Begg's tests were applied to evaluate publication bias. Trial sequential analysis (TSA) and false-positive report probability (FPRP) were performed. Nine case-control studies containing 4202 sALS cases and 4444 healthy controls were included in the meta-analysis. A significant association of the DPP6 (rs10260404) variant with an increased sALS risk in overall pooled subjects under allelic model [C allele vs. T allele, OR = 1.149, 95% CI (1.010-1.307), p-value = 0.035], dominant model [CC + CT vs. TT, OR = 1.165, 95% CI (1.067-1.273), p-value = 0.001], and homozygote comparison [CC vs. TT, OR = 1.421, 95% CI (1.003-2.011), p-value = 0.048] were observed. Moreover, in subgroup analysis by nationality, remarkable associations were detected in Dutch, Irish, American, and Swedish under allelic, dominant, and homozygote models. Additionally, stratification analysis by ethnicity exhibited an association with sALS risk among Caucasians and Americans under different genetic models. Interestingly, none of the models found any significant association with Asians. The present meta-analysis indicates that DPP6 (rs10260404) polymorphism could be a candidate risk factor for sALS predisposition.

The pertinence of gastric cancer and interleukin 10–819 single nucleotide polymorphisms: a meta-analysis and systematic review

PurposeCytokines regulate the interaction between the immune system and malignant tumors. Among them, interleukin-10 (IL-10) is a multifunctional anti-inflammatory cytokine mainly produced by immune cells. The correlation between gastric cancer and T/C single nucleotide polymorphism (SNP) of interleukin-10 (IL-10) promoter−819(rs1800871)was opaque and remained to be determined. We aim to explore the pertinence of gastric cancer and SNP of interleukin 10–819 by meta-analysis via five statistical models.MethodsDatabases including PubMed, Cochrane Library, Embase, the Scopus, and Google Scholars were comprehensively retrieved for the eligible studies on the related topic from inception to March 2022. Odds ratios (ORs) were generated for dichotomous variants by meta-analysis in each model via STATA 17.0 MP. The statistical models comprised recessive model, over-dominant model, allele model, co-dominant model and dominant model. Subgroup analysis was performed to investigate the difference across races as well as the source of heterogeneity if necessary.ResultsEventually a total of 15 articles reporting 7779 patients were enrolled in our study. There were 2383 patients and 5396 controls, collectively. There was no correlation between gastric cancer and IL-10 819 in recessive model, co-dominant model or dominant model, and subgroup analysis showed that Asian, Latin American and Caucasian had no correlation with the risk of gastric cancer. In the allelic model, there was significant correlation between gastric cancer and IL-10 819 (OR = 3.96%, 95%CI: 3.28 to 3.78). In the over-dominant model, there is no correlation between gastric cancer and IL-10 819, but subgroup analysis uncovered significant vulnerability of Asian people with regard to gastric cancer.ConclusionsIn our study, both Asians, Latin Americans, and Europeans showed an increased risk of gastric cancer in the allelic model, whereas only Asians showed significant susceptibility in the super dominant model. Of course, more large cohort studies are needed to confirm our results.

Association of Interleukin-17A and Interleukin-17F Gene Polymorphisms with Atopic Dermatitis in Chinese Children.

Background: Atopic dermatitis (AD) is a chronic, recurrent inflammatory disease associated with an unbalanced immune response in the upper layers of the skin tissue, mostly starting in childhood. As important factors in gene expression regulation, polymorphisms in interleukin (IL)-17A and IL-17F may be associated with the susceptibility and severity of AD. Methods: Blood samples and clinical information were obtained from 132 patients with AD and 100 healthy children. Using multiplex polymerase chain reaction and next-generation sequencing, five potential single-nucleotide polymorphisms (SNPs) of IL-17A and IL-17F were genotyped in all participants. The relationship between SNPs and susceptibility to or severity of AD was examined by analyzing haplotypes and genetic models. Results: The IL-17A rs3819025 polymorphism was substantially associated with higher AD risk in both the allele model (p = 0.03; odds ratio [OR] = 1.76; confidence interval [CI]: 1.05-2.95) and the dominant model (p = 0.04, OR = 1.85; CI: 1.03-3.33). There was no correlation between AD susceptibility and the IL-17A (rs2275913 and rs4711998) or IL-17F (rs763780 and rs12203736) SNPs (all p > 0.05). Additionally, the five IL-17A and IL-17F SNPs did not significantly differ across the mild-to-moderate and severe subgroups (all p > 0.05). Conclusions: The IL-17A/rs3819025 polymorphism was linked to the development of AD, whereas the IL-17F polymorphism was unrelated to the susceptibility to and severity of AD. The IL-17A polymorphism may provide valuable information to speculate on the susceptibility to AD in Chinese Han children.

The linkage between IL-6 rs1800797 variant and breast cancer susceptibility in Bangladeshi women: A case-control study.

Breast cancer is one of the deadliest diseases affecting women in Bangladesh, and its prevalence is increasing year by year. Although several IL-6single nucleotide polymorphisms have been implicated in BC susceptibility and prognosis in various studies, no research has been done to investigate the relationship between breast cancer and IL-6in Bangladeshi women. This investigation aimed to explore the linkage between the rs1800797 variant of IL-6and the susceptibility to breast carcinoma among women in Bangladesh. The IL-6rs1800797 variant was genotyped in 218 subjects (110 cases and 108 controls) using the tetra-primer ARMS-PCRmethod. The statistical analysis was applied utilizing the SPSS software version 24.0. UALCAN database was used for IL-6 mRNA analysis, and genotype-based gene expression was retrieved from GTEx Portal. This study found a significant link between IL-6rs1800797 variants and increased chance of breast cancer across different genetic inheritance models, including additive model 1 (AGvs. GG: OR = 2.16, p = 0.035); dominant model (AG + AA vs. GG: OR = 2.26, p < 0.05); overdominant model (AGvs. GG + AA: OR = 2.08, p < 0.05); and allelic model (A vs. G: OR = 2.15, p < 0.05). However, an insignificant association of breast cancer was found in both additive model 2 (AAvs. GG: OR = 2.91, p > 0.05) and the recessive model (AAvs. GG + AG: OR = 2.52, p > 0.05). Under the analysis of the probability of false positive reports, no significant values were found in different models when the OR was 1.5, and the prior probability was 0.25. A significant relationship was found between the IL-6rs1800797 genetic variant and the risk of breast cancer. However, the findings of the study should be further investigated with a larger sample size to validate the correlation.

Effects of Ninjurin 2 polymorphisms on susceptibility to coronary heart disease

ABSTRACT Objective The aim of this study was to explore the effects of Ninjurin 2 (NINJ2) polymorphisms on susceptibility to coronary heart disease (CHD). Methods We conducted a case-control study with 499 CHD cases and 505 age and gender-matched controls. Five single nucleotide polymorphisms (SNPs) in NINJ2 (rs118050317, rs75750647, rs7307242, rs10849390, and rs11610368) were genotyped by the Agena MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis to assess the association of NINJ2 polymorphisms and CHD risk-adjusted for age and gender. What’s more, risk genes and molecular functions were screened via protein-protein interaction (PPI) network and functional enrichment analysis. Results Rs118050317 in NINJ2 significantly increased CHD risk in people aged more than 60 years and women. Rs118050317 and rs7307242 had strong relationships with hypertension risk in CHD patients. Additionally, rs75750647 exceedingly raised diabetes risk in cases under multiple models, whereas rs10849390 could protect CHD patients from diabetes in allele, homozygote, and additive models. We also observed two blocks in NINJ2. Further interaction network and enrichment analysis showed that NINJ2 played a greater role in the pathogenesis and progression of CHD. Conclusion Our results suggest that NINJ2 polymorphisms are associated with CHD risk.

Interleukin-18 Gene Polymorphisms and Rheumatoid Arthritis Susceptibility: An Umbrella Review of Meta-Analyses.

This study systematically analyzes the association between interleukin-18 (IL-18) gene polymorphisms and rheumatoid arthritis (RA) susceptibility. The electronic databases Ovid MEDLINE, Ovid Excerpta Medica Database, and Cochrane Library were searched to identify meta-analyses that included case-control studies reporting IL-18 gene polymorphisms and RA susceptibility. Data were reanalyzed using Review Manager Software 5.1, and Mantel-Haenszel random effects were applied for the five genetic models: allelic, recessive, dominant, homozygote, and heterozygote. The effect size of odds ratios (ORs) and their corresponding 95% confidence interval (CI) were calculated. A total of seven meta-analyses with poor quality were included. The IL-18 polymorphisms -607 A/C, -137 C/G, -920 T/C, and -105 C/A have been reported. With weak evidence, IL-18 -607 A/C polymorphisms were associated with a reduced risk of RA susceptibility using the allele model (OR = 0.76, 95% CI: 0.61 - 0.93, p=0.01), dominant model (OR = 0.67, 95% CI: 0.50 - 0.90, p=0.008), homozygote model (OR = 0.57, 95% CI: 0.35 - 0.91, p=0.02), and heterozygote model (OR = 0.71, 95% CI: 0.54 - 0.93, p=0.01) in the overall population. IL-18 gene polymorphisms and RA susceptibility are affected by ethnicity: With weak evidence, IL-18 -137 C/G polymorphisms were related to reduce RA susceptibility in the Asian population (allele model: OR = 0.59, 95% CI: 0.40 - 0.88, p=0.01; dominant model: OR = 0.57, 95% CI: 0.37 - 0.89, p=0.01; heterozygote model: OR = 0.60, 95% CI: 0.38 - 0.94, p=0.03). IL-18 -607 A/C gene polymorphisms are a protective factor for RA susceptibility in the overall population, and IL-18 -137 C/G gene polymorphisms are a protective factor for RA susceptibility in the Asian population. Further studies are needed to confirm these results owing to the limitations of the included studies.

Assessing the impact of novel risk loci on Alzheimer's and Parkinson's diseases in a Chinese Han cohort.

Overwhelming evidence points to that genetic factors contributing to the development of Alzheimer's disease (AD) and Parkinson's disease (PD). Genome-Wide Association Study (GWAS) has come a long way in the last decade. So far, a large number of GWAS studies have been published on neurological diseases and many other diseases, providing us with a wealth of genetic information and unique biological insights. Genomic DNA was extracted from both patients' and controls' peripheral blood samples utilizing the Blood Genome Extraction Kit. Single nucleotide polymorphisms (SNPs) were genotyped employing the enhanced multiple ligase detection reaction (iMLDR) technology. A case-control study was conducted, involving 211 AD patients, 508 PD patients (including 117 with dementia), and 412 healthy individuals. Age and sex stratification analysis revealed that rs871269/TNIP1 was associated with LOAD (p = 0.035), and rs5011436/TMEM106B was associated with AD in males (p = 0.044) in the genotype model. In the allele model, rs871269/TNIP1 was found to be associated with PD in the Chinese Han population (p = 0.0035, OR 0.741, 95% CI 0.559-0.983), and rs708382/GRN was identified as a risk factor for Parkinson's disease dementia (PDD) in the Chinese Han population (p = 0.004, odds ratio (OR) 0.354, 95% confidence interval (CI) 0.171-0.733). However, no significant associations with AD or PD were observed for the remaining four loci (rs113020870/AGRN, rs6891966/HAVCR2, rs2452170/NTN5, rs1761461/LILRB2) in terms of allele or genotype frequencies. This study identifies rs871269/TNIP1 as a potential risk factor for both LOAD and PD, rs708382/GRN as a risk factor for PDD, and rs5011436/TMEM106B as associated with AD in males when stratified by age.

Association Between VEGF-460C/T Gene Polymorphism and Risk of Diabetic Retinopathy in Type 2 Diabetes Mellitus: A Meta-Analysis.

The aim of the study was to investigate the relationship between VEGF-460C/T polymorphism and susceptibility to diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) by meta-analysis. A comprehensive search was conducted across six databases until September 2023 to identify studies examining the association between VEGF-460C/T polymorphism and susceptibility to DR. Data process was performed by Stata 15.0 software. Eight studies were included, involving 1463 patients with DR. In the overall analysis, the difference was statistically significant only in the homozygous model (CC vs. TT: OR=1.86, p=0.048). A subgroup analysis of 6 papers with genotype frequency satisfying HWE in the control group indicated significant differences among the allele (C vs. T: OR=1.34, p=0.037), recessive (CC vs. CT+TT: OR=1.96, p=0.022) and homozygous (CC vs. TT: OR=2.28, p=0.015) models. However, in the dominant and heterozygous models, the difference was not statistically significant. The sensitivity of the HWE-based subgroup analysis showed that the conclusions in other gene models except the heterozygote model were not robust. This meta-analysis indicated that VEGF-460C/T gene polymorphism is associated with susceptibility to DR in T2DM. Allele C and genotype CC at the VEGF-460C/T locus are associated with an increased risk of DR in T2DM. However, considering that the results are not robust, more trials involving more rigorous design are needed to verify the findings of this review in the future.

The Influence of ESR2 Gene Polymorphisms on Susceptibility to Hepatitis B Virus-Related Chronic Hepatitis, Liver Cirrhosis, and Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) represents an estrogen-dependent tumor. The action of estrogen is regulated via estrogen receptor (ER). Polymorphisms in ERα gene, ESR1, are known to be related to HCC susceptibility among people carrying chronic hepatitis B (CHB). But the effect of ERβ on HCC is still largely unclear, and studies about the genetic variability of ESR2 and HCC are rare. For understanding ESR2's effect on HCC, this work tested two polymorphisms in the ESR2 gene promoter as well as the associations with CHB, HCC, and hepatitis B virus (HBV)-related liver cirrhosis (LC) among the Guangxi population. This work enrolled a total of 137 CHB, 136 LC, and 149 HBV-related HCC patients, together with 146 normal subjects. ESR2 polymorphisms rs3020449 and rs2978381 were examined using the SNaPshot genotyping technique. The AG genotype and dominant model of rs3020449 were related to the decreased CHB susceptibility. In both the overall and subgroup analyses, no associations were observed with the remaining models in all patient groups (those with CHB, HBV-related LC, and HCC), but associations were found between the dominant (TC+CC vs TT) and allele models (C vs T) of rs2978381 and increased HBV-related LC and HCC susceptibility, but not CHB. These findings suggest that rs3020449 polymorphism of ESR2 gene makes great contribution to the decreased CHB risk and that rs2978381 significantly contributed to higher risks of HBV-related LC and HCC.

Association of ACE*(Insertion/Deletion) Variant with the Elevated Risk of Preeclampsia Among Gestational Women.

The renin-angiotensin-aldosterone system has an indispensable function in the uteroplacental circulation, placental growth, and blood pressure optimization. The angiotensin I converting enzyme (ACE) gene is a critical integrator for electrolyte balance, and water retention, along with inhibiting preeclampsia. The main goal of this pertaining study is to assess the contribution of ACE*(Ins/Del) variant with the susceptibility for preeclampsia with focus on the severity of the disease among gestational hypertensive women. This retrospective study included 225 participants [125 PE gestational women, and 100 normotensive healthy controls] matching with age, and geographical region. PE women classified into 82 early-onset PE women, accompanied with 43 late-onset PE women. Additionally, PE women categorized into 59 mild PE women, together with 66 severe PE women. The genotyping and characterization of ACE*(Ins/Del) variant were applied using the PCR technique. Our findings indicated higher frequency of the ACE*(Del/Del) genotype and ACE*(D allele) with elevated risk of preeclampsia compared to normotensive controls under recessive (OR = 2.09, and p-value = 0.007), and allelic (OR = 1.75, and p-value = 0.012) models. In addition, testing logistic regression revealed that the levels of endothelin-1 and malondialdehyde exposed significant difference for the ACE*(Del/Del) genotype among early-onset and late-onset PE women (p-value = 0.024, and 0.23, respectively). Furthermore, carriers of the ACE*(Del/Del) genotype observed statistically significant with lower sodium concentrations among severe PE women (p-value = 0.034). The ACE*(Del/Del) genotype and ACE*(D allele) were associated with increased risk preeclampsia among gestational women. Furthermore, early-onset PE and late-onset PE were correlated with endothelin-1 and malondialdehyde concentrations among Egyptian women.