Abstract Background Diabetic kidney disease (DKD) denotes the structural and functional alterations in renal tissues occurring as a diabetic complication. Growth arrest-specific 6 (GAS6) and its receptor AXL have been identified as biological markers linked to DKD. Single nucleotide polymorphisms (SNPs) serve as valuable markers for assessing polygenic diseases like DKD. This study investigated the association of GAS6 rs8191974, rs9577873, AXL rs2304232, and rs4802113 with DKD in Egyptians. Methods SNP selection was based on previous literature, and potential functional impact according to Ensembl Variant Effect Predictor. The SNPs were genotyped in 70 type 2 diabetic patients with normal kidney functions and diabetic duration > 5 years as the DM group, 70 type 2 diabetic patients showing microalbuminuria (30–300 mg/day) as the DKD group, and 60 apparently healthy controls, using TaqMan genotyping assays. Glycosylated hemoglobin, plasma creatinine and fasting plasma glucose levels were determined spectrophotometrically. Urinary albumin, plasma GAS6 and AXL levels were assayed using ELISA kits. Results Genotyping of the SNPs in cases and controls fitted the Hardy–Weinberg equilibrium ( p > 0.05). The genotypic frequencies as compared between cases and controls for rs8191974 ( p = 0.609, χ 2 = 2.703), rs9577873 ( p = 0.916, χ 2 = 4.611), rs2304232 ( p = 0.215, χ 2 = 5.799) and rs4802113 ( p = 0.742, χ 2 = 6.828) revealed no statistically significant differences. Genotypic variation in the analyzed SNPs within each group did not influence plasma GAS6 or AXL levels. No significant associations were noticed between studied parameters and SNP alleles. Conclusion No significant association was found between GAS6 rs8191974, GAS6 rs9577873, AXL rs2304232, or AXL rs4802113 and the development of type 2 diabetes or DKD in Egyptians. To date, this is the first genetic study assessing GAS6/AXL gene variants association with DKD in the Egyptian population.

Acanthamoeba castellanii is a free-living amoeba that is emerging as a model organism for the study of eukaryotic microbiology. This species is one of the most widely studied members of the Amoebozoa and is both an important grazer in soil communities and an opportunistic human pathogen; A. castellanii is thus of evolutionary, ecological, and biomedical significance. Despite its potential as a lab workhorse, the genome biology of A. castellanii is complex and poorly understood. Polyploidy is a common feature of many amoebozoan genomes, and members of the genus Acanthamoeba are no exception; they appear to be not only polyploid, where genome copy number is inflated beyond the conventional haploid and diploid states, but also aneuploid, i.e. with inter-chromosomal copy number variation. To better understand aneuploidy in A. castellanii and how it may vary over time and between closely related strains, we analyzed nanopore and Illumina sequence datasets from several wild-type and mutant A. castellanii lines, with a focus on quantifying single nucleotide polymorphism and structural variant allele frequencies across chromosome-scale scaffolds. Sequence depth of coverage was also considered. Our findings suggest that intragenomic chromosome copy number is highly variable in Acanthamoeba, consistent with a considerable degree of aneuploidy, but is predominantly stable in laboratory culture and on the evolutionary scale of the species or genus.

ABSTRACT Background Multiple studies have associated PTGER4 polymorphisms with susceptibility to several autoimmune diseases, particularly ankylosing spondylitis (AS)—a condition strongly linked to the onset of acute anterior uveitis (AAU). Given this association, we investigated whether PTGER4 variants are associated with AAU susceptibility in Chinese populations. Methods To identify PTGER4 disease susceptibility loci, we recruited 904 healthy subjects (AS-AAU-) and 402 AAU patients (AAU+AS-). Genotyping used the MassArray system (iPLEX Gold). SNP allele and genotype frequency differences between groups were assessed with chi-square tests. To account for multiple comparisons, we applied the Bonferroni correction. Additionally, haplotype analysis and stratified analysis were conducted to further explore potential genetic relationships. Results The two PTGER4 single nucleotide polymorphisms (SNPs) loci (rs10440635, rs4133101) exhibited no significant correlation with susceptibility to AAU. No significant differences in haplotype frequencies were observed between AAU groups and controls following stratified analysis. Conclusion Our findings demonstrate that the two loci, rs10440635 and rs4133101 in PTGER4, were not found to be associated with susceptibility to AAU in this population. Specifically, for rs10440635, the odds ratio (OR) was 0.924 (95% CI: 0.757–1.128, p = 0.438), and for rs4133101, the OR was 0.918 (95% CI: 0.777–1.085, p = 0.314). Even after stratifying the analysis by HLA-B27 status, no statistically significant association was observed. To further elucidate the potential role of PTGER4 in these conditions, additional studies with larger sample sizes, broader genetic variants, and more diverse ethnic populations are warranted.contribution of PTGER4 to these diseases.

Association of NLRP3 (rs4612666) polymorphism in gingival crevicular fluid with symptomatic irreversible pulpitis and asymptomatic apical periodontitis

The quality of food products can be influenced by the breed or variety of origin, as well as the composition ratios in mixtures of breeds or varieties. We present a method to estimate the breed or variety composition ratio in food samples using single-nucleotide polymorphism (SNP) allele frequency data and a non-negative least squares (NNLS) optimization approach. To evaluate the method's performance, we simulated two datasets (cow and cacao) containing simulated samples with specified breed or variety composition ratios, then compared the predicted ratios to the actual values. Results show that the method estimates the composition ratios of breeds and varieties with significantly lower average absolute error than a uniform probability baseline (4.1 % vs 24.6 % for cows, p-value = 1.9 × 10-17; and 11.8 % vs 24.6 % for cacao, p-value = 1.1 × 10-8). Additionally, the accuracy of identifying the majority breed or variety in a sample is also significantly higher than assuming equal probability of breed mixing (92 % vs 28 % for cows and 72 % vs 28 % for cacao). The corresponding code for the breed or variety composition ratio estimation is available in the Github repository: (https://github.com/IBPA/NNLS-SNP).

ABSTRACTBackgroundIn our previous study, the minor T allele of the rs7858836 C/T single‐nucleotide polymorphism (SNP) in the ASTN2 gene, which encodes astrotactin 2, was associated with reduced fentanyl requirements after laparoscopic‐assisted colectomy and after mandibular osteotomy. In this study, we investigated the effects of this SNP on pain‐related phenotypes in patients who underwent laparoscopic gynecologic surgery (LGS).MethodsWe studied 333 Japanese women, 21–69 years, who underwent LGS at Juntendo University Hospital between 2017 and 2019. We evaluated associations between SNP genotypes and postoperative pain‐related phenotypes, including fentanyl requirements, rescue analgesic requirements, and the average pain scores on an 11‐point Numeric Rating Scale (NRS) during the 24‐h postoperative period. Patients with the TT or CT genotype were compared with those with the CC genotype using the Mann–Whitney test or χ2 test. Values of p < 0.05 were considered statistically significant.ResultsThe minor T allele frequency was 34.1%. Patients with the CT or TT genotype reported significantly lower average NRS pain scores (median, 1.6 vs. 2.0; p = 0.031) and required fewer rescue analgesics (5.5% vs. 15.0%; p = 0.003) compared to those with the CC genotype. Postoperative fentanyl requirements did not differ between the two groups (p = 0.940).ConclusionThe minor T allele of the rs7858836 SNP was significantly associated with lower postoperative pain intensity, albeit only slightly, and decreased the need for rescue analgesics under comparable fentanyl dosing conditions, potentially reflecting lower pain sensitivity. However, the magnitude of the effect was less than our previous findings.

Understanding the genetic basis of growth and fat deposition is crucial for improving beef productivity in Kalmyk cattle, a breed well adapted to the extreme climatic conditions of Kazakhstan. The present study aimed to determine the effects of single-nucleotide polymorphisms (SNPs) in the CRTC2 and ELOVL6 genes on intramuscular fat content and to evaluate their associations with growth and meat quality traits in 18-month-old Kalmyk heifers raised under different environmental conditions. A total of 400 clinically healthy Kalmyk heifers (200 from LLP "Qazaq Asyldary" and 200 from LLP "Agrofirma Turikpen") were examined. All animals originated from closed breeding herds, and only unrelated individuals without common ancestors to the third generation were included. Zootechnical measurements- live weight, withers height, chest depth, chest girth, and body length-were performed twice by a trained specialist. Backfat thickness and musculus longissimus dorsi depth were measured postmortem. Blood samples were collected for genomic DNA extraction using the GeneJET purification kit, and DNA quality was assessed by Nanodrop, Qubit, and agarose gel electrophoresis. Target fragments of CRTC2 and ELOVL6 were amplified (150-200 bp) and sequenced on an ABI 3500 system. SNP identification, allele frequencies, and genotyping were performed by alignment to the Bos taurus ARS-UCD1.2 reference genome. Statistical analyses were conducted in RStudio using linear and mixed models with "farm" as a random effect. Only one informative polymorphism, g.133528A>G in ELOVL6, was detected. Three genotypes (AA, AG, GG) were observed, with the heterozygous AG genotype showing significantly higher live weight, greater body length, and improved linear measurements compared to AA and GG. No significant associations were detected with backfat thickness or muscle depth. The g.133528A>G polymorphism in ELOVL6 positively influences growth traits without increasing fatness, aligning with the naturally lean phenotype of Kalmyk cattle. The AG genotype may serve as a promising marker for selecting faster-growing animals in marker-assisted breeding programs.

BackgroundPredictive biomarkers for anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) therapy are needed. Here, we validated the role of PD-1 single nucleotide polymorphisms (SNPs) in predicting the development of immune-related adverse events (irAEs) in patients with advanced cancer treated with anti-PD-1/PD-L1-based immunotherapy and defined the molecular mechanisms underlying the role of identified SNP candidate.MethodsBlood samples, clinical-pathological characteristics, survival outcomes and irAEs were collected from two cohorts of patients: (1) patients with advanced cancer treated with anti-PD-1/PD-L1 alone and (2) patients with advanced non-small cell lung cancer (NSCLC) treated with anti-PD-1 in combination with platinum-based chemotherapy with or without anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) therapy. PD-1 SNPs including rs2227981, rs7421861, rs11568821, rs36084323, rs2227982 and rs10204525 were genotyped and correlated with clinical-pathological characteristics and irAEs. Putative miRNAs binding to PD-1 SNP candidate were identified by in silico analysis. Validation of miRNA binding to PD-1 SNP allele specificity as well as evaluation of the induced PD-1 modulation was performed in vitro using patient-derived peripheral blood mononuclear cells (PBMCs). Susceptibility of non-cancer cells to immune cells incubated with anti-PD-1 based on PD-1 SNP allele specificity and miRNA modulation was performed by co-culturing non-cancer human epidermal keratinocyte (HaCaT) cells and bronchial epithelial BEAS-2B cells with human leukocyte antigen (HLA)-matched PBMCs, obtained from patients with cancer treated with anti-PD-1/PD-L1-based immunotherapy and carrying a different PD-1 SNP.ResultsMost of the analyzed PD-1 SNPs were not associated with the development of irAEs. In contrast, rs10204525 exhibited a significant association with the occurrence of both grade 1–2 and 3–4 irAEs in both cohorts of patients. Specifically, patients carrying C/C had a higher rate of irAEs as compared with those carrying C/T. rs10204525 mapped on 3′ untranslated region (3’-UTR) region of PD-1. miR-4717-3p bound to rs10204525 based on its allele specificity. Modulation of miR-4717-3p expression as well as of miR-4717-3p binding to rs10204525 differentially regulated PD-1 expression and induction in PMBCs harboring C/C or C/T genotypes as well as their ability to recognize and destroy HLA-matched HaCaT cells, even more in the presence of anti-PD-1 therapy. Specifically, PBMCs carrying a C/T genotype displayed a significantly lower ability to recognize and destroy non-cancer cells as compared to those carrying C/C. These results were further validated by co-culturing of both BEAS-2B and HaCaT non-cancer cells with PBMCs carrying differential rs10204525 genotypes, isolated from additional patients with cancer, incubated with anti-PD-1 or anti-PD-1 in combination with anti-CTLA-4 therapy.ConclusionsThese findings have high clinical relevance since they define rs10204525 binding to miR-4717-3p-mediated PD-1 expression and induction as a mechanism modulating the reactivity of immune cells to non-cancer cells as well as a novel biomarker for predicting irAEs in patients with advanced cancer treated with anti-PD-1/PD-L1-based immunotherapy.

Proteomic genotyping for individual human identification: Inferring SNPs in the absence of DNA evidence.

ABSTRACTObjectivePrenatal single‐nucleotide polymorphism (SNP)‐based cell‐free DNA (cfDNA) screening can identify genome‐wide paternal uniparental disomy (GW‐UPDpat), including cases with complete hydatidiform mole with a coexisting fetus (CHMCF), those with placental mesenchymal dysplasia (PMD) and those with a mosaic/chimeric GW‐UPDpat syndrome. Our objective was to review laboratory data and pregnancy outcome for SNP‐based cfDNA screening tests with results compatible with GW‐UPDpat and a normal cell line.MethodsThis was a retrospective study of all cfDNA screening results from a single commercial laboratory between June 2014 and November 2023 that were reported as twins or triploidy, with apparent GW‐UPDpat. Two‐dimensional representations of the relative ratios of SNP alleles (SNP plots) were used to identify and quantify the proportion of cfDNA from the mole (‘molar fraction’) and that from the coexisting non‐molar pregnancy (‘fetal fraction’). Test referral and follow‐up information, including ultrasound findings, laboratory testing and pregnancy outcome, were reviewed.ResultsOf 5 699 009 tests reviewed, 89 were reported as twins or triploidy, with apparent GW‐UPDpat. Retrospective review of SNP plots excluded 12 cases that were reinterpreted as triploidy with an extra set of paternal chromosomes. Of the remaining 77 cases, 24 had follow‐up pregnancy information available, and of these, 21 (87.5%) had ultrasound and/or pathology findings that were consistent with CHMCF. The fetal cfDNA fraction was often very low (≤ 2% in 28 cases). The molar cfDNA fraction was in the range of 10–58%. Fetal sex was male in 35 cases, female in 40 cases and uncertain in two cases. No case showed clear evidence of a Y‐chromosome in the GW‐UPDpat line. All 77 cases had isodisomy; none showed clear evidence of regions of heterodisomy.ConclusionsSNP‐based cfDNA screening can help to identify CHMCF and distinguish between CHMCF and triploidy. For CHMCF, early detection is important for evaluating the risk of adverse outcome and gestational trophoblastic neoplasia. Some of our test‐positive cases could have included unrecognized PMD or mosaic/chimeric GW‐UPDpat syndrome. These preliminary observations do not allow assessment of the sensitivity or positive predictive value of this test. © 2025 Natera, Inc. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The association between single nucleotide polymorphisms in NLRP gene and diabetic nephropathy.

ABSTRACT Background The pathogenesis of lipodystrophy in people living with HIV (PLWHIV) receiving antiretrovirals appears to be multifactorial and may involve genetic factors; however, it is not yet fully understood. We verified the association between single nucleotide polymorphisms in the APOC3-rs2854116, ESR2-rs3020450, HFE-rs1799945 and MMP1-rs1799750 genes and lipodystrophy and its subtypes in PLWHIV receiving antiretroviral. Methods Design: cross-sectional study. Lipodystrophy definition was based on self-report. Genotyping of the polymorphisms was performed using real-time polymerase chain reaction. Results Lipodystrophy was reported in 204/404 participants (51%), being 89/204 with mixed lipodystrophy, 72/204 with lipohypertrophy, and 43/204 with lipoatrophy. There was no association between APOC3, HFE, and MMP1 polymorphisms and lipodystrophy. The frequency of AA genotype (p=0.004/OR=3.33/CI=1.52–7.29) and of A allele (p=0.031/OR=1.72/CI=1.08–2.75) of the ESR2 polymorphism was higher in individuals with lipoatrophy compared to those without lipodystrophy. In the multivariate analysis, viral load >40copies/mL (p=0.037/OR=2.52/CI=1.03–6.91) and current use of zidovudine (p=0.007/OR=2.97/CI=1.32–6.54) were associated with lipoatrophy. Conclusion Participants with lipoatrophy had higher frequency of the AA genotype and the A allele of the ESR2-rs3020450 polymorphism. In addition, viral load >40 copies/mL and current use of zidovudine were associated with lipoatrophy, suggesting a potential involvement of this genetic variant in the pathogenesis of lipoatrophy in PLWHIV receiving antiretroviral.

Background and Aims: Immune checkpoint inhibitors (ICIs) have significantly improved survival rates for patients with metastatic melanoma. However, these treatments can lead to immune-related adverse events (irAEs), including hepatitis. This exploratory study sought to identify tumour single-nucleotide polymorphisms (SNPs) associated with the risk of ICI-induced hepatitis in melanoma patients. Methods: The study cohort comprised 69 patients with malignant melanoma treated with ICIs at several hospitals in Madrid, Spain. DNA was extracted from formalin-fixed paraffin-embedded tumour biopsies and SNP genotyping was conducted using a MassARRAY platform. Results: Significant associations were found between hepatitis risk and 4 of the 20 SNPs examined. A possible risk effect was shown for the variant GABRP SNP alleles rs11743438 and rs11743735. Among patients homozygous for these variant alleles (v/v), significantly higher proportions developed hepatitis, 75% and 71.4%, respectively, compared to 32.8% and 21.4, respectively, not developing hepatitis (p = 0.046; p = 0.013). However, in the same genotype group comparisons, the RGMA SNP rs4778080 seemed to have a protective effect, as 100% of patients who developed hepatitis were not in the v/v group for this allele (p = 0.043). Additionally, in genotype group comparisons wt/wt versus wt/v + v/v, the PACRG SNP rs55733913 was also associated with a higher risk of ICI-induced hepatitis: 66.7% of patients with hepatitis versus 22.8% without hepatitis in genotype group wt/v + v/v (p = 0.041). Conclusions: This exploratory study identifies candidate tumour SNPs as possible biomarkers to predict the risk of ICI-induced hepatitis, warranting their validation in larger patient cohorts.

Introduction: Previous studies, including our research, provide critical insights on the contamination of food, water and environment in the Southern African Development Community (SADC) with diarrhoeagenic Escherichia coli (DEC). This study used whole-genome sequencing to investigate the genetic diversity, virulence-associated factors and antimicrobial resistance (AMR) patterns of DEC isolated from children under 5 years old and food sources in Maputo and compared these findings with publicly available DEC genome assemblies from the Southern Africa region. Methods: Whole-genome sequence data from 11 DEC isolates from food, children under 5 and water sources in Maputo, Mozambique, were analysed alongside 125 publicly available DEC genomic assemblies from the SADC region. The latter were retrieved from the EnteroBase database (http://enterobase.warwick.ac.uk) and included isolates previously collected from food, animals and environmental sources. Genomic analyses were performed using the online pipelines provided by the Centre for Genomic Epidemiology (CGE), Denmark. Unsupervised hierarchical clustering was applied to visualize patterns in genetic diversity, AMR, virulence-associated genes and plasmid content using the R software. Results: Clustering based on single nucleotide polymorphism (SNP) and core genome multilocus sequence typing (cgMLST) alleles revealed associations based on geographic locations, sample niche, pathovar and O:H antigen, pointing to evolutionary relatedness between the clades with principal coordinate analysis uncovering this accounted for 27.55% of the genetic diversity. Virulence-associated genes encoding for attaching and effacing (eae) (63.97%), heat-labile toxin (LT) (25.00%) and Shiga toxin 1 (Stx1) (15.44%) were most abundant, with an inverse association between genes encoding for the presence of LT and eae. Resistance to folate pathway antagonists (sulfamethoxazole-55.9%), β-lactamases (amoxicillin, ampicillin and piperacillin-all 54.4%) and aminoglycoside (streptomycin-55.1%) was most abundant. Conclusions: The study revealed region-specific lineages, evidence of horizontal gene transfer and the clustering patterns suggest both localized and cross-border transmission. The study provides insightful evidence on DEC transmission patterns associated with antimicrobial and disinfectant resistance and associated virulence factors.

Introduction. Chemotherapy remains a cornerstone treatment for most non-Hodgkin lymphoma (NHL) patients, yet it is frequently associated with significant adverse effects that compromise their quality of life. Emerging evidence highlights that genetic factors, particularly single nucleotide polymorphisms (SNPs), play a critical role in determining individual variability in treatment responses and susceptibility to drug-related complications.Aim of this study: to identify SNPs associated with chemotherapy-induced adverse events in NHL through advanced bioinformatics approaches, enabling personalized therapeutic strategies to mitigate risks.Material abd Methods. This study leveraged the PharmGKB database to identify SNPs associated with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone. SNPs meeting inclusion criteria (Level of Evidence 1A-3, p&lt;0.01) were prioritized for functional impact analysis using PolyPhen-2 scores. Data extraction and computational analysis utilized SNPnexus, HaploReg v4.2, Ensembl Genome Browser (GRCh37), and PharmGKB. The methodology employed a descriptive approach, relying exclusively on secondary data sources.Results. This study identified 11 SNPs that may be important for hematological toxicity, liver damage, and nausea risk. These genes are SLC22A16, GSTP1, NAT2, ATM, ABCB1, CYP2B6, XRCC1, ERCC1, MUTYH PIK3R2, and PNPLA3. In terms of priority and risk, the most significant variants were rs738409 (PNPLA3), rs12210538 (SLC22A16), rs2229109 (ABCB1), and rs56022120 (PIK3R2). The distribution of SNP alleles is more common in European populations than in Asians or Africans.Conclusion. For the first time, we found SNPs that indicate an increase in drug side effects. These SNPs rs738409, rs12210538, rs2229109 and rs56022120 increase the severity of NHL patients during chemotherapy. In order to ensure that these biomarkers can be used in clinical practice and to support the creation of precision medicine strategies, additional clinical validation is needed.

Protein and total sugars intake modulate the rs9939609 single nucleotide polymorphism effect at the fat mass and obesity-associated gene on body composition.

BackgroundWheat (Triticum aestivum L.) cultivation suffers from significant yield loss owing to diseases such as Fusarium head blight (FHB) and powdery mildew (PM). Utilization of host resistance is an effective strategy for controlling diseases. Fhb7 and Pm21 are derived from wild relatives of wheat, which confer broad-spectrum resistance to FHB and PM, respectively, and can be used in breeding through marker-assisted selection. Kompetitive Allele Specific polymerase chain reaction (KASP) is a homogeneous fluorescence-based technology, which identifies single nucleotide polymorphisms (SNP), and is suitable for marker-assisted selection (MAS) in large-scale breeding. However, KASP typically identifies the alleles of a single SNP, which limits the efficiency of pyramiding multiple genes during breeding.ResultsIn this study, we developed and applied a novel multiplex KASP (Multi-KASP) system that enabled concurrent detection of two distinct genes in a single reaction. The Multi-KASP system increased the flexibility of primer requirements and differentiated genes using only basic fluorescent cassettes, thereby significantly enhancing genotyping efficiency while ensuring high specificity and accuracy. This system accurately distinguished homozygous and heterozygous genotypes for both genes, which was validated by comparison with conventional marker detection. Phenotyping showed that polymerization of Fhb7 and Pm21 using the multi-KASP system enhanced resistance to FHB and PM in the wheat breeding program.ConclusionsA cost-effective Multi-KASP genotyping system, capable of simultaneously detecting two distinct genes in a single reaction, is an efficient and convenient solution for molecular breeding. The system demonstrates high potential for enhancing the efficiency of MAS in wheat breeding for resistance to FHB and PM.

Background Certain genes present variants associated with molar-incisor hypomineralization (MIH) pathogenesis, especially genes encoding enamel development proteins related to morphogenesis, immune response, and hormone transcription and reception, demonstrating that MIH is likely a gene-environment issue with multiple genes having small individual effects.Objective To evaluate the association between single nucleotide polymorphisms (SNPs) and MIH.Methodology A sample of 90 children with MIH and 262 children without MIH were included in this study. Calibrated examiners diagnosed MIH (Kappa≥0.75) using the European Academy of Paediatric Dentistry (EAPD) criteria and modified DDE index in clinical exams. SNPs in the IL-6 (rs2069840 and rs2069833), ESR (rs9340799, rs1256049, rs4986938, and rs2234693), VDR (rs739837 and rs2228570), and 5-HTT genes (rs1042173 and rs38133034) were genotyped by real-time polymerase chain reaction from oral mucosa cells collected. Associations between MIH and SNPs genotypes (recessive and dominant models) and allele frequencies were tested using the chi-square test. Odds ratio (OR) and confidence intervals (CI) were calculated. A significance level of 5% was adopted. Genotypes were tested by the Hardy–Weinberg Equilibrium using chi-square.Results In rs4986938 (ESR2 gene), children with CT/TT presented significantly lower odds of MIH than CC (OR=0.57, CI 95% [0.35-0.92]). There was no significant association between MIH and other evaluated genes.Conclusion The genetic polymorphism in the ESR gene is associated with MIH, suggesting that MIH etiology presents a polygenetic involvement.

ObjectiveAlcohol is metabolized to acetaldehyde by alcohol dehydrogenases (ADH) and subsequently to acetate by aldehyde dehydrogenases (ALDH). Single nucleotide polymorphisms (SNPs) in ADH1B, ADH1C and ALDH2 genes lead to haplotypes encoding isozymes which influence development of alcoholism. The distribution of these haplotypes in Uganda has not been documented. The aim of this study was to determine genotype, allele, and haplotype frequencies of SNPs in ADH1B, ADH1C, and ALDH2 genes in Uganda.ResultsFive SNPs: ADH1B (rs1229984 and rs2066702), ADH1C (rs1693482 and rs698) and ALDH2 (rs671) were analyzed by PCR-restriction fragment length polymorphism assays in 250 samples. The frequencies of the fast-metabolizing alleles ADH1C*1, ADH1B*3, and ADH1B*2 were 49.6%, 18.2% and 0.2% respectively. The nonprotective allele ADH1B*1 had a high frequency of 81.6% and ADH1C*2 was 10.6%. A novel allele ADH1C*new (Arg271Val349) comprising G at ADH1C rs1693482and G at ADH1C rs698 was identified with a frequency of 39.8%. Of the seven ADH1B–ADH1C haplotype combinations identified, ADH1B*1-ADH1C*1 was the most prevalent (48.4%). Notably ADH1B*1–ADH1C* new, had the second highest frequency (25.2%). Our study provides the first data on novelADH1B-ADH1C haplotypes in alcohol metabolizing genes in the Ugandan population.

Background: Metabolic syndrome is the clustering of multiple factors that directly increase the risk of cardiovascular disease and type 2 diabetes. Two missense mutations of the DYRK1B gene, including H90P and R102C, were recently found to co-segregate with a rare autosomal-dominant form of metabolic syndrome, called abdominal obesity-metabolic syndrome (AOMS3). Affected individuals developed early-onset cardiovascular disease, hypertension, central obesity, and diabetes. Conclusions: Objectives: The DYRK1B R102C mutation significantly increases the key gluconeogenic enzyme and glucose-6-phosphatase. Methods: In this research, we evaluated the association between single nucleotide polymorphism (SNP) rs4508194 and metabolic syndrome in individuals with DYRK1B gene mutations. The rs450819 genotypes are determined by polymerase chain reaction in 121 heterozygote and homozygote subjects in the DYRK1B gene. PCR products were sequenced, and then a survey was conducted on the sequences. Data were analyzed with chi-square statistical testing and Prism6 and SPSS software. Results: The results do not show a correlation between these SNP alleles and increased metabolic syndrome risk in individuals suffering from metabolic syndrome and its risk factors. Conclusions: The rs450819 SNP genotypes do not play a role in the development of metabolic syndrome.