Association between the ABCA1 (R219K) polymorphism and lipid profiles: a meta-analysis

Conflicting evidence was found about the relationship between lipid profiles and R219K polymorphism in adenosine triphosphate-binding cassette exporter A1 (ABCA1) gene. In this study, four meta-analyses were conducted to assess the effect of R219K on lipid levels, including high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol, total cholesterol, and triglycerides (TG). A total of 125 samples of 87 studies (about 60,262 subjects) were included. The effect of each study was expressed using the standard mean difference (SMD) and 95% confidence interval (95% CI) and pooled by meta-analysis in the random-effects model. Subgroup and meta-regression analyses were conducted to explore potential heterogeneity sources. The overall pooled effect showed the following results. (1) The R219K was significantly associated with HDLC level (SMD = − 0.25 mmol/L, 95%CI − 0.32 to − 0.18, z = − 6.96, P < 0.01, recessive genetic model). People with different genotypes had significantly different HDLC levels under the recessive, codominant and dominant genetic models (all Ps < 0.01). (2) A weak and indeterminate relationship between R219K and TG level was observed (SMD = 0.18 mmol/L, 95%CI 0.06–0.30, z = 3.01, P < 0.01, recessive genetic model). These findings suggested that R219K was associated with HDLC and TG levels, which might implicate a promising clinical application for lipid-related disorders, though the influences of race, health status, BMI, and other heterogeneity sources should be considered when interpreting current findings. The protocol was registered at PROSPERO (registration number: CRD42021231178).

The Association of CTLA-4 rs231775 and rs3087243 Polymorphisms With Latent Autoimmune Diabetes in Adults: A Meta-analysis

BackgroundPolymorphisms rs231775 and rs3087243 of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) gene have been associated with risk of latent autoimmune diabetes in adults (LADA). However, the results were inconsistent. The purpose of this study was to quantitatively assess the relationship between polymorphisms rs231775 and rs3087243 of CTLA-4 and LADA in a larger pooled population by performing a meta-analysis. MethodsSystematic search for eligible studies was conducted in PubMed, Web of Science, and Embase. Case-control studies containing genotype frequencies of polymorphisms rs231775 or rs3087243 of CTLA-4 gene were selected, and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the associations between polymorphisms of CTLA-4 and LADA in allelic genetic model, dominant genetic model, and recessive genetic model. ResultsA total of eleven studies, in which five studies reported rs231775, two studies reported rs3087342, and four studies reported both rs231775 and rs3087243, were identified. Among them, one study wasn’t included in the following meta-analysis because the distribution of genotypes in the control group didn’t comply with Hardy-Weinberg equilibrium. Significant associations with susceptibility to LADA were detected for rs231775 (785 cases and 3435 controls, allelic genetic model OR 1.53, 95%CI 1.22-1.92; dominant genetic model OR 2.16, 95%CI 1.43-3.28; recessive genetic model OR 1.49, 95%CI 1.13-1.97) and for rs3087243 (820 cases and 4824 controls, allelic genetic model OR 1.26, 95%CI 1.03-1.55; dominant genetic model OR 1.11, 95%CI 0.88-1.40; recessive genetic model OR 1.41, 95%CI 1.07-1.86) in overall population. Further subgroup analyses for ethnicity (Asian, Caucasian, and African) have also indicated the positive association between rs231775 and LADA. As for rs3087243, subgroup analyses detected the association between polymorphism and LADA in Caucasian population under recessive model. ConclusionsPolymorphisms rs231775 and rs3087243 of CTLA-4 gene are potential risk factors for LADA and may serve as novel genetic biomarkers of LADA.

Association between the IL-10-1082G/A, IL-10-819T/C and IL-10-592A/C polymorphisms and Brucellosis susceptibility: a meta-analysis

Brucellosis is a widespread zoonosis caused by small bacteria of the genus Brucella. The promoter polymorphisms of IL-10 (-1082 loci, -819 loci and -590 loci) are closely related to the production of IL-10, leading to the alteration of development and pathogenesis of Brucellosis. However, the previous results were controversial. In the present study, we conduct the meta-analysis to get a more precise result of IL-10 polymorphisms with Brucellosis risk. The quality of the studies was assessed according to a predefined scale. The odds ratio (OR) and 95% confidence interval (CI) were counted to evaluate the association strength. No significant association was found between position -1082 loci or -590 loci polymorphism and Brucellosis risk. The significant association was found in Asian population of position -819 (T vs. C: OR 0.60, 95% CI 0.44–0.82, P = 0.001), homozygote comparison (TT vs. CC: OR 0.24, 95% CI 0.09–0.62, P = 0.003) and recessive genetic model (TT vs. TC/CC: OR 0.22, 95% CI 0.05–0.91, P = 0.036). The present meta-analysis demonstrates that IL-10-819 loci polymorphism is not associated with Brucellosis risk of Caucasian population but may contribute a decreased risk to Asian population. And neither IL-10-1082 loci nor -592 loci polymorphism is associated with Brucellosis risk.

Association between TLR2 + 2477G/A polymorphism and bacterial meningitis: a meta-analysis

Toll-like receptor 2 (TLR2) is a key member of TLRs, which is crucial in the initial inflammatory response against bacteria. TLR2, is also the initial barrier against bacterial infection and plays an important role in recognising a variety of bacterial lipoproteins. Several studies have been performed to investigate the TLR2 + 2477G/A polymorphism and bacterial meningitis susceptibility. Unfortunately, the results of previous studies were controversial. Therefore, we performed a meta-analysis to derive a more precise estimation of the association. The association between the TLR2 + 2477G/A polymorphism and bacterial meningitis susceptibility was assessed by odds ratios together with their 95% confidence intervals (CI). Six studies were enrolled in the present meta-analysis. Overall, no significant association between TLR2 + 2477G/A polymorphism and bacterial meningitis risk were found under allele contrast (A vs. G: OR = 1.15, 95% CI = 0.93–1.43, P = 0.202), recessive genetic model (AA vs. AG/GG: OR = 1.12, 95% CI = 0.90–1.41, P = 0.313). The significant association was found between TLR2 + 2477G/A polymorphism and pneumococcal meningitis risk under allele contrast (A vs. G: OR = 1.54, 95% CI = 1.01–2.36, P = 0.046), recessive genetic model (AA vs. AG/GG: OR = 1.63, 95% CI = 1.03–2.57, P = 0.035). We conclude that TLR2 + 2477G/A polymorphism is not associated with meningococcal meningitis risk but contributes an increased risk of pneumococcal meningitis.