The special status accorded to elite athletes stems from their uncommon genetic potential to excel in world-class power sports (PS). Genetic polymorphisms have been reported to influence elite PS status. Reports of associations between the α-actinin-3 gene (ACTN3) R577X polymorphism and PS have been inconsistent. In light of new published studies, we perform a meta-analysis to further explore the roles of this polymorphism in PS performance among elite athletes. Multi-database literature search yielded 44 studies from 38 articles. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used in estimating associations (significance threshold was set at P^a ≤ 0.05) using the allele-genotype model (R and X alleles, RX genotype). Outlier analysis was used to examine its impact on association and heterogeneity outcomes. Subgroup analysis was race (Western and Asian) and gender (male/female)-based. Interaction tests were applied to differential outcomes between the subgroups, P-values of which were Bonferroni corrected (P_{interaction BC}). Tests for sensitivity and publication bias were performed. Significant overall R allele effects (OR 1.21, 95% CI 1.07–1.37, P^a = 0.002) were confirmed in the Western subgroup (OR 1.11, 95% CI 1.01–1.22, P^a = 0.02) and with outlier treatment (ORs 1.12–1.20, 95% CIs 1.02–1.30, P^a < 10⁻⁵–0.01). This treatment resulted in acquired significance of the RX effect in Asian athletes (OR 1.91, 95% CI 1.25–2.92, P^a = 0.003). Gender analysis dichotomized the RX genotype and R allele effects as significantly higher in male (OR 1.14, 95% CI 1.02–1.28, P^a = 0.02) and female (OR 1.58, 95% CI 1.21–2.06, P^a = 0.0009) athletes, respectively, when compared with controls. Significant R female association was improved with a test of interaction (P_{interaction BC} = 0.03). The overall, Asian and female outcomes were robust. The R allele results were more robust than the RX genotype outcomes. No evidence of publication bias was found. In this meta-analysis, we present clear associations between the R allele/RX genotype in the ACTN3 polymorphism and elite power athlete status. Significant effects of the R allele (overall analysis, Western and female subgroups) and RX genotype (Asians and males) were for the most part, results of outlier treatment. Interaction analysis improved the female outcome. These robust findings were free of publication bias.

Genetics plays a role in determining potential for athletic ability (AA) and sports performance (SP). In this study, AA involves comparing sedentary controls with competitive athletes in power and endurance activities as well as a mix between the two (SP). However, variable results from genetic association studies warrant a meta-analysis to obtain more precise estimates of the association between PPARGC1A Gly482Ser polymorphism and AA/SP. Multi-database literature search yielded 14 articles (16 studies) for inclusion. Pooled odds ratios (ORs) and 95% confidence intervals (CI) were used to estimate associations. Summary effects were modified based on statistical power. Subgroup analysis was based on SP (power, endurance and mixed) and race (Caucasians and Asians). Heterogeneity was assessed with the I² metric and its sources examined with outlier analysis which dichotomized our findings into pre- (PRO) and post-outlier (PSO). Gly allele effects significantly favoring AA/SP (OR > 1.0, P < 0.05) form the core of our findings in: (i) homogeneous overall effect at the post-modified, PSO level (OR 1.13, 95% CI 1.03–1.25, P = 0.01, I² = 0%); (ii) initially homogeneous power SP (ORs 1.22–1.25, 95% CI 1.05–1.44, P = 0.003–0.008, I² = 0%) which precluded outlier treatment; (iii) PRO Caucasian outcomes (ORs 1.29–1.32, 95% CI 1.12–1.54, P = 0.0005) over that of Asians with a pooled null effect (OR 0.99, 95% CI 0.72–1.99, P = 0.53–0.92) and (iv) homogeneous all > 80% (ORs 1.19–1.38, 95% CI 1.05–1.66, P = 0.0007–0.007, I² = 0%) on account of high statistical power (both study-specific and combined). In contrast, none of the Ser allele effects significantly favored AA/SP and no Ser-Gly genotype outcome favored AA/SP. The core significant outcomes were robust and showed no evidence of publication bias. Meta-analytical applications in this study generated evidence that show association between the Gly allele and AA/SP. These were observed in the overall, Caucasians and statistically powered comparisons which exhibited consistent significance, stability, robustness, precision and lack of bias. Our central findings rest on association of the Gly allele with endurance and power, differentially favoring the latter over the former.

Tendons and ligaments are common sites of musculoskeletal injuries especially during physical activity. The multifactorial etiology of tendon-ligament injury (TLI) includes both genetic and environmental factors. The genetic component could render influence on TLI risk to be either elevation or reduction. Inconsistency of reported associations of the collagen type V alpha 1 chain (COL5A1) polymorphisms, mainly rs12722 (BstUI) and rs13946 (DpnII), with TLI warrant a meta-analysis to determine more precise pooled associations. Multi-database literature search yielded eight articles (11 studies) for inclusion. Pooled odds ratios (ORs) and 95% confidence intervals were used to estimate associations. Heterogeneity of outcomes warranted examining their sources with outlier treatment. All rs12722 effects indicated reduced risk (OR < 1.0). The significant outcomes (ORs 0.59–0.77, p = 0.0009–0.04) in the pre-outlier analysis were non-heterogeneous (p > 0.10). The non-significant and heterogeneous (ORs 0.63–0.98, p = 0.13–0.95; up to I2 = 86%) pre-outlier rs12722 and rs13946 results became significant (ORs 0.32–0.78, p = 10−5−0.01) and heterogeneity eliminated (I2 = 0%) with outlier treatment. Significant associations (ORs 0.26–0.65, p = 0.002–0.03) were also observed in other COL5A1 polymorphisms (rs71746744 and rs16399). Sensitivity analysis deemed all significant outcomes to be robust. In summary, COL5A1 polymorphisms reduce the risk of TLI among Caucasians. These findings are based on the evidence of significance, homogeneity, consistency, and robustness. Additional studies are warranted to draw more comprehensive conclusions.

The changes in the severe acute respiratory syndrome coronavirus 2 and the tapering of immunity after vaccination have propelled the need for a booster dose vaccine. We aim to evaluate B and T cell immunogenicity and reactogenicity of mRNA-1273 COVID-19 vaccine (100 µg) as a third booster dose after receiving either two doses of inactivated COVID-19 vaccine (CoronaVac) or two doses of viral vector vaccine (AZD1222) in adults not previously infected with COVID-19. The anti-receptor-binding-domain IgG (anti-RBD IgG), surrogate virus neutralization test (sVNT) against the Delta variant, and Interferon-Gamma (IFN-γ) level were measured at baseline, day (D)14 and D90 after vaccination. In D14 and D90, the geometric means of sVNT were significantly increased to 99.4% and 94.5% inhibition in CoronaVac, respectively, whereas AZD1222 showed inhibition of 99.1% and 93%, respectively. Anti-RBD IgG levels were 61,249 to 9235 AU/mL in CoronaVac and 38,777 to 5877 AU/mL in AZD1222 after D14 and D90 vaccination. Increasing median frequencies of S1-specific T cell response by IFN-γ concentration were also elevated in D14 and were not significantly different between CoronaVac (107.8–2035.4 mIU/mL) and AZD1222 (282.5–2001.2 mIU/mL). This study provides evidence for the high immunogenicity of the mRNA-1273 booster after two doses of CoronaVac or AZD1222 in the Thai population.

Background: Brain‐derived neurotrophic factor (BDNF) has been proposed to play a role in chronic alcohol consumption. However, studies investigating the association of single nucleotide polymorphisms (SNPs) in the BDNF gene with alcohol use disorder (AUD), including alcohol dependence, have obtained inconsistent results. This meta‐analysis aims to examine the role of BDNF SNPs (rs6265, rs16917204, rs7103411, and rs11030104) in the risk of AUD.Materials and Methods: A multidatabase search identified 17 articles (20 studies) for inclusion. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate associations using standard genetic models (homozygous, recessive, dominant, and codominant). Significant associations were defined as those with a p‐value ≤ 0.05 after applying the Bonferroni correction (p^BC). Subgroup analysis was conducted based on ethnicity (Caucasian and Asian populations). Sources of heterogeneity were investigated through outlier treatment and meta‐regression analysis. Only significant outcomes were further subjected to sensitivity analysis and assessment of publication bias.Results: This meta‐analysis generated four significant pooled ORs, representing the core outcomes, all of which indicated reduced risks. Overall, the results indicated a significant association between the BDNF polymorphism and the risk of AUD in homozygous (OR = 0.72, 95% CIs = 0.60–0.85, p^BC = 0.0038) and codominant (OR = 0.84, 95% CIs = 0.78–0.91, p^BC = 0.0019) model. In subgroup analysis by ethnicity, homozygous (OR = 0.59, 95% CIs = 0.44–0.78, p^BC = 0.0057) and recessive (OR = 0.61, 95% CIs = 0.46–0.81, p^BC = 0.0133) models of BDNF polymorphisms were significantly associated with a reduced risk of AUD in Caucasians. However, no significant associations were found in Asians. Meta‐regression analysis did not identify any covariates that significantly contributed to the observed heterogeneity. The core significant associations were robust and showed no evidence of publication bias.Conclusion: The current meta‐analysis suggests that the examined BDNF SNPs have a protective effect in the overall analysis (homozygous and codominant) and in the Caucasians subgroup (homozygous and recessive) while the Asians exhibited no effects of BDNF SNPs on AUD. BDNF polymorphisms might serve as a protective factor against the risk of AUD and could be useful markers in the clinical genetics of AUD.

Reported associations of the interferon gamma (IFNG) +874T/A (rs2430561) polymorphism with post-kidney transplantation allograft rejection (AR) have been inconsistent, prompting a meta-analysis to obtain more precise estimates. Eighteen articles (22 studies) were included in the meta-analysis. Operating on the hypothesis that IFNG rs2430561 either increases or reduces AR risk, we used a genetic model-free approach to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Subgrouping was based on ethnicity (white, Middle Eastern, black, and mixed) and rejection type (ACR: acute rejection and CHR: chronic rejection). Quality of the associative effects was assessed with sensitivity treatment and test for publication bias. The overall analysis in the dominant model indicated increased risk (OR = 1.26; Pa = .02) was validated in the ACR subgroup (OR = 1.29; Pa = .01), which contrasted with the CHR subgroup, with a nonsignificant effect indicating reduced risk (OR = 0.83; Pa = .68). Only the black subgroup showed significant increased risk (OR = 2.87; Pa = .04), but the association was tenuous on account of low sample size (n = 2) and imprecise effect (95% CI, 1.07-7.73). Increased risk associations (overall and ACR) of IFNG rs2430561 with AR is significant, robust, statistically powered, and lacking bias. Contrasting ACR (1.3-fold increased risk) and CHR (7% protective) effects may be clinically relevant in the genetics of renal transplantation.