Diabetes mellitus (DM) is a chronic systemic disease characterized by a multifactorial nature, which may lead to several macro and microvascular complications. Diabetic retinopathy (DR) is one of the most severe microvascular complications of DM, which can result in permanent blindness. The mechanisms involved in the pathogenesis of DR are multiple and still poorly understood. Factors such as dysregulation of vascular regeneration, oxidative and hyperosmolar stress in addition to inflammatory processes have been associated with the pathogenesis of DR. Furthermore, compelling evidence shows that components of the immune system, including the complement system, play a relevant role in the development of the disease. Studies suggest that high concentrations of mannose-binding lectin (MBL), an essential component of the complement lectin pathway, may contribute to the development of DR in patients with DM. This review provides an update on the possible role of the complement system, specifically the lectin pathway, in the pathogenesis of DR and discusses the potential of MBL as a non-invasive biomarker for both, the presence and severity of DR, in addition to its potential as a therapeutic target for intervention strategies.

Single nucleotide polymorphisms (SNPs) have been reported to play an important role in the etiology of dental caries. The aim of this research was, through a systematic review, to identify SNPs recently associated with dental caries in pediatric populations. We included studies performed in humans up to 18 years of age that evaluated the relationship between SNPs and dental caries from 2017 to 2022. Articles that covered other study variables were excluded. PubMed, ScienceDirect and Web of Science were used to search for information and the included articles were evaluated with one of the Joanna Briggs Institute\'s tools. Twenty-five articles were selected, 60% of which were given high methodological quality. A total of 10,743 research subjects, ranging in age from 20 months to 17 years, participated in the study. The SNPs considered risk factors were identified in the genes miRNA202, VDR, AMELX, TUFT1, KLK4, MBL2, ENAM, DEFB1, HLA-DRB1, TAS1R1, DSPP, RUNX2 and MMP13; those considered protective factors were identified in the genes MMP20, AMBN, MMP9, TIMP2, TNF-α, VDR, IL1B, ENAM and HLA-DRB1. This systematic review presents the genetic polymorphisms that are associated with the etiology of caries in children and adolescents, some of which act as risk factors and others as protective factors against the disease.
Se ha reportado que los polimorfismos de nucleótido único (SNPs) juegan un papel importante en la etiología de la caries dental. El objetivo de esta investigación fue, a través de una revisión sistemática, identificar los SNPs asociados recientemente a la caries dental en poblaciones pediátricas. Se incluyeron estudios realizados en humanos de hasta 18 años de edad que evaluaron la relación entre los SNPs y la caries dental, publicados desde el 2017 hasta el 2022. Se excluyeron los artículos que abarcaron otras variables de estudio. PubMed, ScienceDirect y Web of Science se utilizaron para la búsqueda de información y los artículos incluidos fueron evaluados con una de las herramientas del Instituto Joanna Briggs. Fueron seleccionados 25 artículos, al 60% de ellos se le otorgó calidad metodológica alta. En total participaron 10,743 sujetos de invetigación, cuyas edades variaron de 20 meses a 17 años. Los SNPs considerados factores de riesgo fueron identificados en los genes miRNA202, VDR, AMELX, TUFT1, KLK4, MBL2, ENAM, DEFB1, HLA-DRB1, TAS1R1, DSPP, RUNX2 y MMP13, los considerados factores de protección se identificaron en los genes MMP20, AMBN, MMP9, TIMP2, TNF-α, VDR, IL1B, ENAM y HLA-DRB1. Esta revisión sistemática expone los polimorfismos genéticos que se encuentran asociados a la etiología de la caries en niños y adolescentes, algunos de los cuales actúan como factores de riesgo y otros como factores de protección ante la enfermedad.

BACKGROUND: Corona virus disease 2019 (COVID-19) is caused by SARS-CoV-2, the pathogenic process of SARS-Cov-2 is related to the angiotensin-2 converting enzyme (ACE-2) on host cells. The genetic polymorphisms among different populations may influence the progression of COVID-19. However, the effects of IFNL4, ACE1, PKR, IFNG, and MBL2 in severe COVID-19 have not been systematically assessed.
METHODS: We will include all relevant English and Chinese studies by searching the following electronic databases: PubMed, MEDLINE, Embase, Web of Science, Scopus, the Cochrane Library, and Google Scholar before March 31, 2022. Two researchers will independently screen and extract the literature. The methodological quality of the included studies will be evaluated by the Cochrane Handbook for Systematic Reviews of Interventions.
RESULTS: This systematic review and meta-analysis will summarize the association of IFNL4, ACE1, PKR, IFNG, MBL2 genetic polymorphisms, and severe COVID-19. The results will be submitted to a peer-reviewed journal once completed.
CONCLUSIONS: The conclusion of our study will provide evidence for the early prevention of severe COVID-19.
UNASSIGNED: CRD42022301735.

BACKGROUND: Leishmaniasis is caused by an intracellular protozoan of the Leishmania genus. Mannose-binding lectin (MBL) is a serum complement protein and recognizes lipoprotein antigens in protozoa and the bacterial plasma membrane. Nucleotide variants in the promoter region and exon 1 of the MBL gene can influence its expression or change its molecular structure.
OBJECTIVE: To evaluate, through a systematic review, case-control studies of the genetic association of variants in the MBL2 gene and the risk of developing leishmaniasis.
METHODS: This review carried out a search in PubMed, Science Direct, Cochrane Library, Scopus and Lilacs databases for case-control publications with six polymorphisms in the mannose-binding Lectin gene. The following strategy was used: P = Patients at risk of leishmaniasis; I = Presence of polymorphisms; C = Absence of polymorphisms; O = Occurrence of leishmaniasis. Four case/control studies consisting of 791 patients with leishmaniasis and 967 healthy subjects (Control) are included in this meta-analysis. The association of variants in the mannose-binding Lectin gene and leishmaniasis under the allelic genetic model, -550 (Hvs. L), -221 (X vs. Y), +4 (Q vs. P), CD52 (A vs. D), CD54 (A vs. B), CD57 (A vs. C) and A/O genotype (A vs. O) was evaluated. International Prospective Register of Systematic Reviews (PROSPERO): CRD42020201755.
RESULTS: The meta-analysis results for any allelic genetic model showed no significant association for the variants within the promoter, the untranslated region, and exon 1, as well as for the wild-type A allele and mutant allele O with leishmaniasis.
CONCLUSIONS: Caution should be exercised when interpreting these results, as they are based on a few studies, which show divergent results when analyzed separately.
CONCLUSIONS: This meta-analysis showed a non-significant association between the rs11003125, rs7096206, rs7095891, rs5030737, rs1800450, and rs1800451 polymorphisms of the Mannose-binding Lectin gene and leishmaniasis in any allelic and heterogeneous evaluation.

The Severe acute respiratory syndrome may be caused by coronavirus disease which has resulted in a global pandemic. Polymorphisms in the population play a role in susceptibility to severity. We aimed to perform a systematic review related to the effect of single nucleotide polymorphisms in the development of severe acute respiratory syndrome (SARS). Twenty-eight eligible articles published were identified in PubMed, ScienceDirect, Web of Science, PMC Central and Portal BVS and additional records, with 20 studies performed in China. Information on study characteristics, genetic polymorphisms, and comorbidities was extracted. Study quality was assessed by the STrengthening the REporting of Genetic Association (STREGA) guideline. Few studies investigated the presence of polymorphisms in HLA, ACE1, OAS-1, MxA, PKR, MBL, E-CR1, FcγRIIA, MBL2, L-SIGN (CLEC4M), IFNG, CD14, ICAM3, RANTES, IL-12 RB1, TNFA, CXCL10/IP-10, CD209 (DC-SIGN), AHSG, CYP4F3 and CCL2 with the susceptibility or protection to SARS-Cov. This review provides comprehensive evidence of the association between genetic polymorphisms and susceptibility or protection to severity SARS-CoV. The literature about coronavirus infection, susceptibility to severe acute respiratory syndrome (SARS) and genetic variations is scarce. Further studies are necessary to provide more concrete evidence, mainly related to Covid-19.

Pneumonia, sepsis, meningitis, and empyema due to Streptococcus pneumoniae is a major cause of morbidity and mortality. We provide a systemic overview of genetic variants associated with susceptibility, phenotype and outcome of community acquired pneumococcal pneumonia (CAP) and invasive pneumococcal disease (IPD).
We searched PubMed for studies on the influence of host genetics on susceptibility, phenotype, and outcome of CAP and IPD between Jan 1, 1983 and Jul 4, 2018. We listed methodological characteristics and when genetic data was available we calculated effect sizes. We used fixed or random effect models to calculate pooled effect sizes in the meta-analysis.
We identified 1219 studies of which 60 studies involving 15,358 patients were included. Twenty-five studies (42%) focused on susceptibility, 8 (13%) on outcome, 1 (2%) on disease phenotype, and 26 (43%) on multiple categories. We identified five studies with a hypothesis free approach of which one resulted in one genome wide significant association in a gene coding for lincRNA with pneumococcal disease susceptibility. We performed 17 meta-analyses of which two susceptibility polymorphisms had a significant overall effect size: variant alleles of MBL2 (odds ratio [OR] 1·67, 95% confidence interval [CI] 1·04-2·69) and a variant in CD14 (OR 1·77, 95% CI 1·18-2·66) and none of the outcome polymorphisms.
Studies have identified several host genetics factors influencing risk of pneumococcal disease, but many result in non-reproducible findings due to methodological limitations. Uniform case definitions and pooling of data is necessary to obtain more robust findings.

In recent years, many studies have demonstrated that the MBL-2 gene polymorphisms may be associated with pulmonary tuberculosis (PTB) susceptibility. Moreover, some studies have shown that serum MBL levels were influenced by the MBL-2 gene polymorphisms and that it plays an important role in tuberculosis infection. However, the results of these studies were inconsistent and underpowered. The current meta-analysis and systematic review aimed to evaluate the association between the MBL-2 gene polymorphisms and serum MBL levels with PTB. Finally, 30 eligible articles were included in the study. The overall results indicated that the MBL-2 rs1800450 (54 A/B) and rs5030737 (52 A/D) polymorphisms were risk factors for PTB, but the MBL-2 rs1800451 (57 A/C) and rs7095891 (+4 P/Q) polymorphisms as protective factors against PTB. No associations were found in the other three polymorphisms (exon 1, rs7096206 (-221 X/Y), and rs11003125 (-550 H/L) of the MBL-2 gene. In addition, we could not detect any significant differences between haplotypes among PTB patients and healthy controls. More important, the meta-analysis results indicated that the serum MBL levels in patients with PTB were significantly lower than those in healthy controls (SMD = 0.43, 95% CI = 0.33-0.52). This study suggested that the MBL-2 gene polymorphisms may be involved in the pathogenesis of PTB, and serum MBL may be a biomarker for the diagnosis of PTB. More rigorous research is needed in the future to confirm these findings further.

Mannose-binding lectin (MBL) is a soluble pattern recognition molecule involved in complement activation. Single nucleotide polymorphisms (SNPs) in the MBL2 gene have been associated with susceptibility to infection, although data in solid organ transplant recipients remains inconclusive. This meta-analysis was primarily aimed at investigating the association between posttransplant bacterial and fungal infection and variant alleles of MBL2 gene SNPs in the promoter/5\' untranslated region and exon 1. Cytomegalovirus (CMV) infection and/or disease were considered secondary outcomes. PubMed, EMBASE, and Web of Knowledge were searched for relevant articles up to August 2018. Eleven studies (comprising 1858 patients) were included, with liver transplant (LT) recipients accounting for 80.4% of the pooled population. As compared to high-MBL expression haplotypes (YA/YA, YA/XA), any MBL-deficient haplotype was associated with an increased risk of posttransplant bacterial and fungal infections (risk ratio [RR]: 1.30; P = .04). Low/null-MBL expression haplotypes (XA/O, O/O) also increased the risk of primary outcome (RR: 1.51; P = .008) and CMV events (RR: 1.50; P = .006). No effect was observed for individual promoter SNPs. In conclusion, MBL-deficient haplotypes are associated with a significant, albeit moderate, increase in the risk of posttransplant infection, with this association being mainly restricted to LT recipients.

Dengue and West Nile viruses are highly cross-reactive and have numerous parallels in geography, potential vector host (Aedes family of mosquitoes), and initial symptoms of infection. While the vast majority (> 80%) of both dengue and West Nile virus infections result in asymptomatic infections, a minority of individuals experience symptomatic infection and an even smaller proportion develop severe disease. The mechanisms by which these infections lead to severe disease in a subset of infected individuals is incompletely understood, but individual host differences including genetic factors and immune responses have been proposed. We sought to identify genetic risk factors that are associated with more severe disease outcomes for both viruses in order to shed light on possible shared mechanisms of resistance and potential therapeutic interventions.
We applied a search strategy using four major databases (Medline, PubMed, Embase, and Global Health) to find all known genetic associations identified to date with dengue or West Nile virus disease. Here we present a review of our findings and a meta-analysis of genetic variants identified.
We found genetic variations that are significantly associated with infections of these viruses. In particular we found variation within the OAS1 (meta-OR = 0.83, 95% CI: 0.69-1.00) and CCR5 (meta-OR = 1.29, 95% CI: 1.08-1.53) genes is significantly associated with West Nile virus disease, while variation within MICB (meta-OR = 2.35, 95% CI: 1.68-3.29), PLCE1 (meta-OR = 0.55, 95% CI: 0.42-0.71), MBL2 (meta-OR = 1.54, 95% CI: 1.02-2.31), and IFN-γ (meta-OR = 2.48, 95% CI: 1.30-4.71), is associated with dengue disease.
Despite substantial heterogeneity in populations studied, genes examined, and methodology, significant associations with genetic variants were found across studies within both diseases. These gene associations suggest a key role for immune mechanisms in susceptibility to severe disease. Further research is needed to elucidate the role of these genes in disease pathogenesis and may reveal additional genetic factors associated with disease severity.

Chronic Obstructive Pulmonary Disease (COPD) impacts differently on patients at similar grades, suggesting that factors other than lung function may influence patients\' experience of the disease. Recent studies have found associations between genetic variations and patient-reported outcomes (PROs). Identifying these associations might be fundamental to predict the disease progression and develop tailored interventions. This systematic review aimed to identify the genetic variations associated with PROs in COPD.
Databases were searched until July 2017 (PROSPERO: CRD42016041639) and additional searches were conducted scanning the reference list of the articles. Two independent reviewers assessed the quality of studies using the Q-Genie checklist. This instrument is composed of 11 questions, each subdivided in 7 options from 1 poor-7 excellent. Thirteen studies reporting 5 PROs in association with genes were reviewed. Studies were rated between \"good quality\" (n = 8) and \"moderate\" (n = 5). The most reported PRO was frequency of exacerbations (n = 7/13), which was mainly associated with MBL2 gene variants. Other PRO\'s were health-related quality of life (HRQOL) (n = 4/13), depressive symptoms (n = 1/13), exacerbation severity (n = 1/13) and breathlessness, cough and sputum (n = 1/13), which were commonly associated with other genetic variants.
Although a limited number of PRO\'s have been related to genetic variations, findings suggest that there is a significant association between specific gene variants and the number/severity of exacerbations, depressive symptoms and HRQOL. Further research is needed to confirm these findings and assess the genetic influence on other dimensions of patients\' lives, since it may enhance our understanding and management of COPD.