The role of SKA2 on affective disorder, post-traumatic stress disorder and suicide behavior: systematic review and in silico analysis.

Genes involved in the hypothalamic-pituitary-adrenal axis may be a robust biomarker of psychiatric disorders. Genetic polymorphisms of the SKA2 gene are associated with several behavioral disorders. In this study, we embarked on a systematic search of all possible reports of genetic association with SKA2 and affective disorder, post-traumatic stress disorder, and suicide behavior; the functional consequences of nsSNPs were explored through computational tools with an in silico analysis. Eight eligible articles were included. Our study identified that SKA2 did not show association with risk of Major Depression Disorder. Epigenetic variation at SKA2 mediates vulnerability to Post-Traumatic Stress Disorder. Studies provide strong preliminary evidence that alterations at the SKA2 gene covary with types of suicide behavior, including suicidal ideation, attempts, and completions. Results from in silico analysis predicted that I22S, I22G, I78T, A15L, D18R, R25L, N42I, Y21S, K14I, K14L, and L60R were the most structurally and functionally significant nsSNPs in SKA2. Amino acid conservation analysis revealed that the amino acids were highly conserved and some dissimilarities of mutant type amino acids from wild-type amino acids such as charge, size, and hydrophobicity were observed. In the future, SKA2 gene have the potential to be evaluated as prognostic biomarkers for diagnosis and research.

Effects of IL-6/IL-6R axis alterations in serum, plasma and cerebrospinal fluid with the schizophrenia: an updated review and meta-analysis of 58 studies.

Studies investigating the association between IL-6/IL-6R axis and schizophrenia (SZ) susceptibility found inconsistent data. To reconcile the results, a systematic review followed by a meta-analysis was performed to assess the associations. This study followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive search of the literature was carried out in July 2022 using electronic databases PubMed, EBSCO, Science Direct, PsychInfo, and Scopus. Study quality was assessed by the Newcastle-Ottawa scale. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effect or random-effect model analysis. Fifty-eight studies were identified, including 4,200 SZ patients and 4,531 controls. Our meta-analysis results showed an increase of IL-6 levels in plasma, serum, or CSF and decreased IL-6R levels in serum in patients under treatment. Further studies are needed to better elucidate the correlation between the IL-6/IL-6R axis and the schizophrenia.

The association of cytokines genes (IL-6 and IL-10) with the susceptibility to schizophrenia: A systematic review and meta-analysis.

Cytokines are among the important effectors and messenger molecules for restoring the homeostasis tissue after an inflammatory response. The association between IL-6 and IL-10 genes polymorphisms with the schizophrenia susceptibility have yielded controversial results. To reconcile the results, a systematic review followed by meta-analysis was performed to assess the association. We carried out literature searches of PubMed, Scopus, EBSCO, and Web of Sciences databases. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to assess the strength of the association. Subgroup analysis, heterogeneity analyses, and publication bias were also calculated in the meta-analysis. A total of 22 case-control studies, consisting of 4,993 schizophrenic patients and 5,195 healthy controls, were included in the meta-analysis. The meta-analysis suggests that the IL-6 rs1800795 polymorphism displays a protective role against schizophrenia, while the IL-10 rs1800896 and rs1800872 polymorphisms confer an increased risk of schizophrenia. Similar results were found in subgroup analysis by ethnicity. We did not find association between IL-10 rs1800871 polymorphism and schizophrenia susceptibility. Finally, this meta-analysis suggested that the dysregulation of cytokines could lead to the pathogenesis of the schizophrenia.

Gene-environment interaction between HPA-axis genes and trauma exposure in the suicide behavior: A systematic review.

Suicide behavior (SB) emerge from complex interactions among traumatic events and multiple genetic factors. We conducted the first systematic review to assess the evidence of a link among trauma exposure, HPA-axis genes, and SB. A systematic search of PubMed, EBSCO, Science Direct, PsychInfo, and Scopus databases on gene-environment interaction, and susceptibility to SB was carried out until February 2022. Our study was prospectively registered in PROSPERO (CRD42022316141). A total of 13 epidemiological studies (11,756 subjects) were included: eight studies focused on traumatic experiences in the childhood and five studies on lifetime trauma exposure. All studies reported a positive association between the trauma exposure with SB. Gene-environment interaction was reported for CRHR1 (n = 6), CRHR2 (n = 2), FKBP5 (n = 2), and CRHBP (n = 1), however, for CRH, NR3C1, MC2R, and POMC genes no found gene-environment effects on SB. Trauma exposure could be one mechanism that links HPA-axis genes activity with the development of SB.

DNA Methylation of Genes Involved in the HPA Axis in Presence of Suicide Behavior: A Systematic Review.

DNA methylation in genes of the hypothalamic-pituitary-adrenal (HPA) axis has been associated with suicide behavior. Through a systematic review, we aimed to evaluate DNA methylation levels of the genes involved in the HPA pathway and their association with suicide behavior. A search of articles was performed using PubMed and Science Direct, EBSCO. The terms included were "DNA methylation", "suicide", "epigenetics", "HPA axis" and "suicide behavior". This systematic review was performed by the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement. Six studies comprising 743 cases and 761 controls were included in this systematic review. The studies included individuals with suicide ideation, suicide attempts or completed suicide and childhood trauma, post-traumatic stress disorder (PTSD), or depression. One study reported hypermethylation in GR in childhood trauma, while two studies found hypermethylation of NR3C1 in childhood trauma and major depressive disorder (MDD). Only one study reported hypermethylation in BNDF in people with MDD. FKBP5 was found to be hypermethylated in people with MDD. Another study reported hypermethylation in CRHBP. SKA2 was reported to be hypermethylated in one study and another study found hypomethylated both in populations with PTSD. CRHR1 was found to be hypermethylated in people with MDD, and the last study found hypomethylation in CRH. Our result showed that patients with suicidal behavior showed a DNA methylation state of genes of the HPA axis in association with psychiatric comorbidity and with adverse events. Genes of the HPA axis could play a role in suicidal behavior associated with adverse events and pathologies. As a result, DNA methylation levels, proteins, and genes involved in the HPA axis could be considered for the search for biomarkers for the prevention of suicidal behavior in future studies.

Association between the HTR1A rs6295 gene polymorphism and suicidal behavior: an updated meta-analysis.

Several association studies have indicated that the HTR1A gene is associated with suicidal behavior (SB). Thus, a systematic assessment of the association of HTR1A was performed based on a literature review and pooled analysis. Four electronic databases were comprehensively searched to find and pinpoint all case-control articles related to this study. When analyzing the genetic association with SB, data were divided into: (A) SB cases vs. healthy controls and (B) SB cases vs. psychiatric controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were assessed as measures of association. Heterogeneity among included studies was analyzed using sensitivity test and Q statistics. Publication bias was also explored by Egger and rank correlation test. Thirteen case-control studies were selected in this meta-analysis, involving 2817 SB patients, 2563 healthy controls and 545 psychiatric controls. In the overall comparison between SB cases and healthy controls, result showed that the rs6295 polymorphisms of HTR1A gene was associated with SB, but only when using the recessive model (OR = 2.21, 95% CI = 1.80-2.71, P < 0.001). In the smaller sample size comparison between SB and psychiatric controls, no significant association was detected with rs6295 in any of the five genetics models tested. The present meta-analysis suggests that rs6295 polymorphism of HTR1A gene could increase the risk for SB. Well-designed studies with more patients will be required to validate these results.

High Serum Levels of IL-6 Are Associated with Suicide Attempt but Not with High Lethality Suicide Attempts: A Preliminary Case-Control Study.

Suicide attempts are an emerging health problem around the world. Increased levels of IL-6 have been associated with suicidal behavior. Therefore, the aims of this study were to evaluate the serum levels of IL-6 in individuals with suicide attempts and a comparison group and to associate the IL-6 levels with the lethality of the suicide attempt. Additionally, we associated the rs2228145 polymorphism of the IL6R gene with suicide attempts or with the IL-6 serum levels. Suicide attempts and their lethality were evaluated using the Columbia Suicide Severity Rating Scale. The serum concentrations of IL-6 were measured by the ELISA technique in individuals with suicide attempts and then compared to a control group. The rs2228145 polymorphism of the IL6R gene was analyzed by real-time polymerase chain reaction. We found elevated serum levels of IL-6 in the suicide attempt group when compared to the control group (F = 10.37, p = 0.002). However, we found no differences of the IL-6 levels between high and low lethality. The IL6R gene polymorphism rs2479409 was not associated with suicide attempts. Our data suggest that IL-6 serum is increased in individuals with suicide attempts.

Association between TPH1 polymorphisms and the risk of suicide behavior: An updated meta-analysis of 18,398 individuals.

Objectives: We aimed to examine the association of TPH1 polymorphisms with the risk of suicide behavior (SB). Design: Systematic review and meta-analysis. Method: All relevant studies that evaluated the association between the A218C (rs1800532), A779C (rs1799913) and A6526G (rs4537731) polymorphisms and the susceptibility to SB published up to September 2021 were identified through a comprehensive systematic search in PubMed, Scopus, EBSCO and Science Direct electronic databases. The association between TPH1 gene polymorphisms and SB was evaluated using inherence models by odds ratio (OR) and 95% confidence interval (CI). Subgroup analyses, heterogeneity analyses, and publication bias were also tested in this meta-analysis. Results: The meta-analysis for TPH1 A218C revealed an increased risk of SB in the dominant model (OR = 1.11, 95%CI 1.01-1.22). We also observed a positive association in the allelic (OR = 1.13, 95%CI 1.05-1.21), homozygous (OR = 1.22, 95%CI 1.06-1.40), heterozygous (OR = 1.21, 95%CI 1.08-1.37) and dominant (OR = 1.21, 95%CI 1.09-1.34) inherence models with the suicide attempt. Additionally, in the heterozygous (OR = 0.84, 95%CI 0.73-0.97) and dominant (OR = 0.79, 95%CI 0.68-0.91) inherence models we detected an association with completed suicide. Based on ethnicity, an association of SB in the European population also was observed (OR = 1.29, 95%CI 1.12-1.51). However, for both A779C and A6526G polymorphisms we did not find evidence of an association with SB. Conclusion: This meta-analysis suggests that the A218C polymorphism of TPH1 gene could be a possible risk factor of SB. Future large-scale studies are required to analyze the molecular mechanisms by which affect the susceptibility of developing suicide behavior.

Mental Health Impact of the COVID-19 Pandemic on Mexican Population: A Systematic Review.

The COVID-19 pandemic has had an impact on mental health in the general population, but no systematic synthesis of evidence of this effect has been undertaken for the Mexican population. Relevant studies were identified through the systematic search in five databases until December, 2021. The selection of studies and the evaluation of their methodological quality were performed in pairs. The Newcastle-Ottawa Scale (NOS) was used for study quality appraisal. The protocol of this systematic review was registered with PROSPERO (protocol ID: CRD42021278868). This review included 15 studies, which ranged from 252 to 9361 participants, with a total of 26,799 participants. The findings show that COVID-19 has an impact on the Mexican population's mental health and is particularly associated with anxiety, depression, stress and distress. Females and younger age are risk factors for development mental health symptoms. Mitigating the negative effects of COVID-19 on mental health should be a public health priority in Mexico.

Possible Association of Cholesterol as a Biomarker in Suicide Behavior.

Suicides and suicidal behavior are major causes of mortality and morbidity in public health and are a global problem. Various authors have proposed changes in lipid metabolism (total cholesterol decrease) as a possible biological marker for suicidal behavior. The objective of this study was to review the studies that have demonstrated a relationship between serum cholesterol levels and suicidal behavior and to describe the possible pathophysiological mechanisms that associate changes in cholesterol concentration and suicidal behavior. Relevant literature related to serum cholesterol levels and suicidal behavior was identified through various database searches. The data from the existing literature present the findings that relate low cholesterol levels and possible pathophysiological mechanisms (neuroinflammation, serotonergic neurotransmission), genes related to cholesterol synthesis, pharmacological treatments that alter lipid metabolism and the possible participation in suicidal behavior. Nevertheless, future research is required to describe how serum cholesterol affects cholesterol metabolism in the CNS to establish and understand the role of cholesterol in suicidal behavior.

Association and Genetic Expression between Genes Involved in HPA Axis and Suicide Behavior: A Systematic Review.

BACKGROUND: Suicide behavior (SB) has been highly associated with the response to stress and the hypothalamic-pituitary-adrenal (HPA) axis. The aim of this study was to summarize the results obtained in genetic studies that analyzed the HPA axis-stress pathway and SB through a systematic review. METHODS: We performed an online search in PubMed, EBSCO, Web of Science, Scopus, and PsycoInfo databases up to May 2021. We followed the PRISMA guidelines for systematic reviews. We included case-control and expression studies that provided data on mRNA expression and single-nucleotide polymorphisms of genes associated with SB. RESULTS: A total of 21,926 individuals participated across 41 studies (not repeats); 34 studies provided data on single-nucleotide polymorphisms in 21,284 participants and 11 studies reported data on mRNA expression in 1034 participants. Ten genes were identified: FKBP5, CRH, CRHBP, CRHR1, CRHR2, NR3C1, NR3C2, SKA2, MC2R, and POMC. CONCLUSIONS: Our findings suggest that key stress pathway genes are significantly associated with SB and show potential as biomarkers for SB.

Oxytocin levels in individuals with schizophrenia are high in cerebrospinal fluid but low in serum: A systematic review and meta-analysis : Oxytocin and Schizophrenia.

Schizophrenia is a debilitating mental illness. Levels of oxytocin have been proposed as a biomarker of schizophrenia; however, the observed levels of oxytocin in individuals with schizophrenia have been inconsistent across studies. We performed a meta-analysis to evaluate oxytocin levels in plasma, serum and cerebrospinal fluid to see if there are statistically different concentrations between individuals with schizophrenia and the comparison group. The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Following the inclusion and exclusion criteria, 14 studies were included in the meta-analysis. The quality of the study was evaluated by the Newcastle-Ottawa Scale (NOS). A random-effects model was performed using the Comprehensive Meta-analysis software with the standardized mean difference (SMD) and 95% confidence intervals (CIs). Serum oxytocin levels in individuals with schizophrenia were significantly lower than that in comparison group (SMD = - 1.74, 95% CI = - 3.22 to - 0.26, p = 0.02) but cerebrospinal fluid oxytocin levels in individuals with schizophrenia were significantly higher than those in the comparison group (SMD = 0.55, 95% CI = 0.05 to 1.04, p = 0.03). Our results suggest that oxytocin levels in cerebrospinal fluid are increased in individuals with schizophrenia but decreased in serum. Therefore, the oxytocin system dysregulation may play a role in the pathophysiology of schizophrenia and it should be measured in more populations for a possible implementation as a biomarker of schizophrenia.

The role of rs242941, rs1876828, rs242939 and rs110402 polymorphisms of CRHR1 gene and the depression: systematic review and meta-analysis.

BACKGROUND: Several studies have evaluated the possible association between polymorphisms or variants in Corticotropin-releasing hormone 1 receptor gene (CRHR1) with depression; however, results remain contradictory and heterogeneous. OBJECTIVE: To our knowledge, we conducted the first comprehensive systematic review and meta-analysis evaluating the association of the CRHR1 gene and the risk of depression. METHODS: A search online was conducted in databases for any CRHR1 genetic association studies in depression. Data were extracted for evaluation of pooled estimates using meta-analytic techniques. Statistical analyses were performed using the Comprehensive Meta-analysis, v2.0 software. RESULT: A total of 1403 cases and 2353 mentally healthy controls were included in this study. We found a significant association of rs242941, rs1876828 and rs242939 variants of the CRHR1 gene with depression. No association of CRHR1 rs110402 and depression was observed. CONCLUSION: Our meta-analysis shows that some variants of the CRHR1 gene (rs242941, rs1876828 and rs242939) might confer susceptibility to depression. Further studies with larger sample sizes need to be conducted.

Knowledge, Emotions and Stressors in Front-Line Healthcare Workers during the COVID-19 Outbreak in Mexico.

The aim of this study was to explore the knowledge, emotions and perceived stressors by healthcare workers who were in contact with infected patients during the COVID-19 outbreak. An online cross-sectional survey was applied. Data were collected from N = 263 healthcare workers in Tabasco State, Mexico. We developed and administered a questionnaire, which consisted of sociodemographic characteristics, plus four sections. The sections evaluated were (1) knowledge of COVID-19; (2) feelings/emotions during the COVID-19 outbreak; (3) factors that caused stress and (4) factors that helped to reduce stress. Surveyed individuals were divided into three groups: physicians, nurses and other healthcare workers. When we evaluated their knowledge of COVID-19 we observed that the majority of healthcare workers in the three groups reported that they knew about COVID-19. Physicians indicated that they felt insecure about practicing their profession (62.5%) due to the high risk of being in contact with SARS-CoV-2. With regards to stressor factors, the risk of transmitting COVID-19 to their families was the main factor causing moderate to high stress (95.4%). Finally, we found that "your profession puts your life at risk" was the only factor associated with feeling nervous and scared (PR: 3.15; 95% CI: 1.54-6.43). We recommended health education campaigns, introductory courses on COVID-19 and other infectious diseases, management protocols and the provision of protection equipment to health workers in order to reduce personal and professional fears of contagion and to improve the health system in Mexico when facing epidemics.

Association between polymorphisms of FKBP5 gene and suicide attempt in a Mexican population: A case-control study.

Five polymorphisms (rs4713916, rs4713902, rs1360780, rs9296158 and rs3800373) of FKBP5 gene were analyzed in a case-control study comprising 423 Mexican individuals (146 individuals with suicide attempt and 277 controls). The SNP's were genotyped using the TaqMan-allelic assay. Genotype and allele frequencies were compared between the two groups, then the association between FKBP5 gene polymorphisms and suicide attempt was analyzed. We found a significant association of rs1360780 T minor allele (All, OR = 1.80, 95 % CI = 1.35-2.41, P = 0.0005; Males, OR = 2.25, 95 % CI = 1.44-3.50, P = 0.0002) as a suicide behavior risk factor. Conversely, rs3800373 C minor allele (All, OR = 0.61, 95 % CI = 0.46-0.83; P = 0.0013; Females, OR = 0.33, 95 % CI = 0.22-0.50; P = 0.0001) and the A-C-T-A-C haplotype (OR = 0.06, 95 % CI = 0.01-0.36; P = 0.002) were significantly associated as protective factors. No association was observed with the other SNP's. Our study suggests that SNP's in FKBP5 gene contribute to suicide behavior pathogenesis.

The role of peripheral cortisol levels in suicide behavior: A systematic review and meta-analysis of 30 studies.

Cortisol can be considered as one biomarker for diagnosis of suicide; nevertheless, several studies have shown conflicting results. This study aimed to evaluate the levels of cortisol in individuals with suicide behavior and controls (healthy or with other psychiatric disorders). Published articles were searched on online databases (PubMed, Scopus and EBSCO). Standardized mean differences (SMD), heterogeneity, publication bias and sensitivity were assessed using the Comprehensive Meta-Analysis (CMA) statistical software. The meta-analysis comprised 30 studies that provided 1775 cases, and 2162 controls (696 healthy individuals and 1465 individuals with other psychiatric diagnoses). The pooled results revealed that cortisol levels were higher in individuals with suicide behavior (SMD = 0.92, 95%CI = 0.26; 1.57, P = 0.006; I2 = 88%, Q < 0.001) than healthy controls. However, individuals with suicide behavior showed decreased levels of cortisol in the morning. Additionally, individuals with suicide behavior showed lower levels of cortisol than psychiatric controls (SMD = -1.79, 95%CI = -3.01; -0.58, P = 0.004, I2 = 89%, Q < 0.001). Morning cortisol levels in individuals with suicide behavior were higher than morning cortisol levels in psychiatric controls. Our updated meta-analysis suggests that peripheral levels of cortisol have a role in suicide behavior.

Quality of life of Latin-American individuals with type 2 diabetes mellitus: A systematic review.

OBJECTIVE: Diabetes mellitus is a serious public health problem that causes a decrease in the patients' quality of life. The present study was aimed to analyze the quality of life of patients with diabetes mellitus in Latin-American population through a systematic review, using the two instruments of greater validity and reliability at international level, SF-36 and WHOQOL. METHODS: We performed extensive searches in Redalyc, SciELO, PubMed, Scopus and Web of Science databases. To delimit our search, we only included countries that are members of the Latin American Association of Diabetes. We identified 2168 articles, where 35 were considered relevant for this systematic review. RESULTS: Our results showed that patients that regularly receive guidance and treatment to control the diabetes, showed better quality of life; in contrast, patients with foot ulcers or comorbidities showed the worse quality of life. CONCLUSION: The current literature analysis suggests that this disease greatly influences in the quality of life of the patients.

Association between APOE polymorphisms and lipid profile in Mexican Amerindian population.

BACKGROUND: Apolipoprotein E (ApoE) is a glycoprotein that plays an important role in lipid homeostasis at both cerebral and systemic levels. Moreover, the differential distribution of APOE gene alleles among different populations, means that ApoE isoforms could have different effects on lipids metabolism. The present study aims to evaluate the relationship between APOE gene alleles and the lipid profile in a Mexican Amerindian (MA) population. METHODS: This study included 1997 MA individuals of different ethnicities distributed throughout different states of Mexico. All individuals underwent anthropometric measurements as well as laboratory tests including fasting glucose (FG), total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). TaqMan® probe genotyping assays were used to genotype APOE. The Kruskal-Wallis test was performed to determine the correlation between APOE gene alleles and genotypes and the biochemical variables measured. RESULTS: Among the biochemical variables analyzed, only the HDL-C and LDL-C levels showed statistical differences (p-value < .05) between individuals carrying different APOE alleles. For HDL-C, individuals carrying the E2 allele had higher HDL-C levels, followed by individuals carrying the E3 allele and carriers of the E4 allele presented the lowest levels of HDL-C (E2 > E3 > E4). This relationship was inversed for LDL-C levels (E2 < E3 < E4). Nevertheless, the difference of HDL-C levels between APOE-E3 and APOE-E4 carriers remained only in obese individuals. CONCLUSIONS: Our results suggest that APOE gene genotypes play an important role in the differential modulation of lipid profiles in the MA population with obesity.

Interleukin 6 (rs1800795) gene polymorphism is associated with cardiovascular diseases: a meta-analysis of 74 studies with 86,229 subjects.

Cardiovascular diseases (CVD) are group of complex and multifactorial pathologies, in which interleukin-6 (IL-6) gene polymorphisms have been associated with several components of the CVD. Thus, in this study, we thoroughly reviewed and meta-analyzed evidence on the association between the IL-6 (rs1800795) gene polymorphism and CVD. We systematically searched in the PubMed, Web of Sciences, and Scopus databases. The analyses were performed using five study groups based on (1) a combined pool of the overall populations, (2) the country of birth, (3) the continent of birth, (4) the diagnosis and (5) both location (country or continent) and diagnosis. The analysis included the allelic, homozygote, heterozygote, dominant and recessive models. The meta-analysis showed that -174G>C (rs1800795) is a risk factor for CVD (allelic: OR=1.06, CI 95%=1.02-1.10. Z p value <0.0001; homozygous: OR=1.11, CI 95%=1.03-1.19, Z p value= 0.002; heterozygous: OR=1.08, CI 95%=1.03-1.21, Z p value= 0.003; dominant: OR= 1.12, CI 95%= 1.07-1.18, Z p value= 0.001) and that this risk increases in the Chinese population. Additionally, we found that carriers of the C allele of 174G>C (rs1800795) polymorphism have an increase in the risk of coronary artery disease under the hereditary models assessed in the study. Using robust data, we found that IL-6 (rs1800795) -174G>C gene polymorphism is associated with CVD risk.

Association of vitamin D receptor polymorphisms and nephrolithiasis: A meta-analysis.

Nephrolithiasis is a complex disease in which its pathophysiology is strongly influenced by genetics. Polymorphisms of the vitamin D receptor (VDR) gene have been reported to be associated with the development of kidney stones which in most cases are composed predominantly of calcium salts. For the purpose of this study, we performed a systematic review and meta-analysis to analyze the association of BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236) and FokI (rs2228570) polymorphisms with nephrolithiasis. A systematic search was performed up to June 2018 using PubMed, Embase and ISI Web of Knowledge databases. The keywords used for the search were "vitamin D receptor or VDR" and "polymorphisms or SNPs" combined with "urolithiasis or nephrolithiasis". A meta-analysis was performed with the results of the selected and included studies. After analyzing 23 publications, we observed that BsmI polymorphism (rs1544410) has a protective association against nephrolithiasis (Allelic model: OR = 0.84, CI 95% 0.73-0.96, Z p-value 0.015; homozygous model: OR = 0.72, CI 95% 0.54-0.97, Z p-value 0.033). Furthermore, we observed that FokI polymorphism (rs2228570) has a decreased risk of nephrolithiasis in the heterozygous model in the presence of heterogeneity (OR = 0.69, CI 95% 0.48-0.99, Z p-value 0.044), as well as in the absence of heterogeneity (OR = 0.81, CI 95% 0.66-0.99, Z p-value 0.045). Additionally, TaqI polymorphism (rs731236) was associated with a decreased risk of nephrolithiasis in the heterozygous model (OR = 0.77, CI 95% 0.63-0.94, Z p-value 0.010), and no overall association was observed with ApaI polymorphism (rs7975232). This meta-analysis provided comprehensive evidence that VDR polymorphisms are associated with upper urinary tract stones incidence and the genetic variants we studied provide protection against nephrolithiasis.