Prevalence of ABO and Rhesus (D) Blood Group and Allelic Frequency at Blood Bank of Nigist Eleni Mohammed Hospital, Ethiopia.

Background: The purpose of this cross-sectional study was to determine the pattern of the ABO and rhesus D (RhD) blood group distribution among voluntary blood donors attending five blood donation centers at Nigist Eleni Mohammed General Hospital in Hossana, Ethiopia. Methods: A total of 1,120 participants who fulfilled the "who can give blood" criteria of the World Health Organization were selected randomly. Blood samples were collected, transported to the laboratory, and analyzed for ABO and RhD typing. The data was analyzed using descriptive statistics and chi-square correlation analysis. Results: The study found that the O blood group was the most prevalent (39.0%), followed by A (32.2%), B (22.5%), and AB (6.4%). When considering both the ABO and Rh blood groups together, 92.9% of blood donors were RhD positive, while only 7.1% were RhD negative. The distribution pattern of the ABO blood groups in Gurage Zone, Hadiya Zone, Kembata Zone, and Silte Zone showed that the O blood group was the most prevalent, followed by A, B, and AB, in that order. Conversely, the ABO blood group distribution pattern in Halaba Zone was A > O > B > AB. Civil servants from different occupational statuses were the most dominant voluntary blood donors, accounting for 53.2%, followed by students from different high schools and universities (41.9%), self-employed individuals (4.1%), and others (0.7%). The ABO blood group system had observed allele frequencies significantly different from the expected frequencies (p = 0.007), while the RhD system did not (p = 0.037). Allele frequencies for A, B, and O in the ABO system were 0.3531, 0.2576, and 0.3893, respectively. Observed frequencies for RhD-positive and RhD-negative alleles were 0.9647 and 0.0531, respectively. Conclusion: This study highlights the regional ABO and RhD blood group variations in Ethiopia, noting disparities from expected ABO allele frequencies, and identifies the O blood group predominance among donors with a high RhD-positive prevalence.

EGR3 Polymorphism Is a Potential Susceptibility Factor of Schizophrenia Risk in a Chinese Population.

Objective: The purpose of this study was to evaluate the association between the single nucleotide polymorphisms (SNPs) (EGR3 rs1996147; EGR4 rs3813226, rs6747506; ERBB3 rs2292238; and ERBB4 rs707284, rs7560730) and the risk of schizophrenia (SZ) in a Chinese population. Materials and Methods: We conducted a case-control study, including 248 patients with SZ and 236 healthy controls matched for age and sex. The Mass-array platform was used to detect all the genotypes of the SNPs. Results: The results revealed that the EGR3 rs1996147 AA genotype was associated with borderline decreased SZ risk (AA vs. GG: adjusted OR = 0.43, 95% CI: 0.18-1.02, p = 0.06). However, no significant correlation was found between the other SNPs and overall SZ risk. Subgroup analysis also failed to show any significant association between all SNPs and the risk of SZ. Conclusion: In summary, this study revealed that the EGR3 rs1996147 AA genotype was associated with a borderline risk for SZ.

The Association Between the 5-Hydroxytryptamine Receptor 2A Gene Variants rs6311 and rs6313 and Obstructive Sleep Apnea in the Iranian Kurdish Population.

Introduction: Sleep is one of the most significant parts of everyone's life. Most people sleep for about one-third of their lives. Sleep disorders negatively impact the quality of life. Obstructive sleep apnea (OSA) is a severe sleep disorder that significantly impacts the patient's life and their family members. This study aimed to investigate the relationship between rs6313 and rs6311 polymorphisms in the serotonin receptor type 2A gene and OSA in the Kurdish population. Materials and Methods: The study's population comprises 100 OSA sufferers and 100 healthy people. Polysomnography diagnostic tests were done on both the patient and control groups. The polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) was used to investigate the relationship between OSA and LEPR gene polymorphisms. Results: Statistical analysis showed a significant relationship between genotype frequencies of patient and control groups of rs6311 with OSA in dominant [odds ratio (OR) = 5.203, p < 0.001) and codominant models (OR = 9.7, p < 0.001). Also, there was a significant relationship between genotype frequencies of patient and control groups of rs6313 with OSA in dominant (OR = 10.565, p < 0.001) and codominant models (OR = 5.938, p < 0.001). Conclusions: Findings from the study demonstrated that the two polymorphisms rs6311 and rs6313 could be effective at causing OSA; however, there was no correlation between the severity of the disease and either of the two polymorphisms.

The Association between Histidine-Rich Glycoprotein rs10770 Genotype and Recurrent Miscarriage in Iranian Women.

Purpose: Recurrent miscarriage (RM) is a significant reproductive concern affecting numerous women globally. Genetic factors are believed to play a crucial role in RM, making the histidine-rich glycoprotein (HRG) gene, a topic of interest due to its potential involvement in angiogenesis. This study is aimed at investigating the association between the HRG rs10770 genotype and RM. Method: Blood samples were collected from a total of 200 women at the beginning of the study. Subsequently, a comparative analysis was conducted between the blood samples of 100 women with a history of RM (case group) and the blood samples of another 100 healthy women (control group). HRG rs10770 genotyping was performed through polymerase chain reaction restriction-fragment length polymorphism (PCR-RFLP), followed by statistical analysis to evaluate the relationship between HRG rs10770 genotype and RM. Results: The results indicated a significant statistical difference between the C/C genotype (OR = 3.32, CI: 1.22-9.04, p = 0.01) and the C/T genotype (OR = 1.24, CI: 0.67-2.30, p = 0.47) in both the case and control groups. Additionally, a significant correlation was observed in the C allelic frequency among RM participants compared to the control group (OR = 1.65, CI: 1.06-2.58, p = 0.02). Conclusion: The study highlights the importance of HRG rs10770 in understanding RM, shedding light on its implications for reproductive health. Furthermore, it became evident that women carrying the homozygous C/C genotype exhibited increased susceptibility to the risk of RM.

Development and characterization of 40 InDel markers from the major histocompatibility complex genes of largemouth bass (Micropterus salmoides).

BACKGROUND: The genetic improvement in growth and food habit domestication of largemouth bass (Micropterus salmoides) have made breakthroughs in past decades, while the relevant work on disease resistance were rarely carried out. Major histocompatibility complex (MHC) genes, which are well known as their numbers and high polymorphisms, have been used as candidate genes to mine disease-resistant-related molecular markers in many species. METHODS AND RESULTS: In present study, we developed and characterized 40 polymorphic and biallelic InDel markers from the major histocompatibility complex genes of largemouth bass. The minor allele frequency, observed heterozygosity, expected heterozygosity and polymorphic information content of these markers ranged from 0.0556 to 0.5000, 0.1111 to 0.6389, 0.1064 to 0.5070, and 0.0994 to 0.3750, respectively. Three loci deviated significantly from Hardy-Weinberg equilibrium, while linkage disequilibrium existed at none of these loci. CONCLUSION: These InDel markers might provide references for the further correlation analysis and molecular assisted selection of disease resistance in largemouth bass.

A quantitative genetic model of background selection in humans.

Across the human genome, there are large-scale fluctuations in genetic diversity caused by the indirect effects of selection. This "linked selection signal" reflects the impact of selection according to the physical placement of functional regions and recombination rates along chromosomes. Previous work has shown that purifying selection acting against the steady influx of new deleterious mutations at functional portions of the genome shapes patterns of genomic variation. To date, statistical efforts to estimate purifying selection parameters from linked selection models have relied on classic Background Selection theory, which is only applicable when new mutations are so deleterious that they cannot fix in the population. Here, we develop a statistical method based on a quantitative genetics view of linked selection, that models how polygenic additive fitness variance distributed along the genome increases the rate of stochastic allele frequency change. By jointly predicting the equilibrium fitness variance and substitution rate due to both strong and weakly deleterious mutations, we estimate the distribution of fitness effects (DFE) and mutation rate across three geographically distinct human samples. While our model can accommodate weaker selection, we find evidence of strong selection operating similarly across all human samples. Although our quantitative genetic model of linked selection fits better than previous models, substitution rates of the most constrained sites disagree with observed divergence levels. We find that a model incorporating selective interference better predicts observed divergence in conserved regions, but overall our results suggest uncertainty remains about the processes generating fitness variation in humans.

Analysis of 26 STR loci (PowerPlex® Fusion 6C System) in a mestizo population from Mexico city.

BACKGROUND: Short tandem repeats (STRs) are the most widely used genetic markers in forensic genetics. Therefore, it is essential to document genetic population data of new kits designed for human identification purposes to enable laboratories to use these genetic systems to interpret and solve forensic casework. However, in Mexico, there are no studies with the PowerPlex Fusion 6C System, which includes 26 STRs (23 autosomal STRs and 3 Y-STRs). METHODS AND RESULTS: 600 DNA samples from Mexico City were subjected to genotyping using the PowerPlex Fusion 6C System. For autosomal STRs, 312 different alleles were observed. Combined PE and PD were 99.999999809866% and 99.99999999999999999999999818795%, respectively. Genetic distances and AMOVA test showed low but significant differentiation between Mexican populations. CONCLUSIONS: The results reported in this work demonstrate the efficacy of this system for human identification purposes in the population studied and justify its possible application in other Mexican Mestizo populations.

IGF2BP2 and IGFBP3 Genotypes, Haplotypes, and Genetic Models Studies in Polycystic Ovary Syndrome.

BACKGROUND: Insulin resistance has been correlated with the genetic diversity within the insulin-like binding proteins genes. Moreover, insulin resistance is one of the key characteristics of the widespread reproductive endocrine condition known as polycystic ovarian syndrome (PCOS). Hence, this study is aimed to determine the association between IGFBP3 and IGF2BP2 gene variants and PCOS risk. METHODS: A total of 300 subjects (150 PCOS cases diagnosed based on Rotterdam ESHRE/ASRM consensus criteria and 150 healthy subjects) were recruited in this case-control cross-sectional study. Tetra-primer amplification refractory mutation system polymerase chain reaction (ARMS-PCR) was used for genotyping rs11705701, whereas genotyping of rs1470579 and rs2854744 was done employing PCR-restriction fragment length polymorphism (PCR-RFLP) technique. RESULTS: The CC and AA+AC genotypes of rs1470579 conferred an increased risk of PCOS in our population. Regarding the rs2854744, an increased risk of PCOS was observed under the codominant homozygous (TT vs. GG) model by 2.54 fold. The C allele of rs1470579 and T allele of rs2854744 enhanced PCOS risk by 1.97 and 1.46 folds, respectively. Haplotype analysis showed that the Ars1470579Ars11705701 haplotype conferred a decreased risk of PCOS (odds ratio = 0.53, 95% confidence interval = 0.34-0.83, p = 0.006). The AC/GG/GT, AA/GA/GT, AC/GA/GG, and AC/GA/GT genotype combinations of rs1470579/rs11705701/rs2854744 were associated with a decreased risk of the disease. CONCLUSIONS: IGF2BP2 rs1470579 and IGFBP3 rs2854744 enhanced PCOS susceptibility in a Southeastern Iranian population. Further investigation involving larger cohorts representing diverse ethnic backgrounds is needed to confirm the current findings.

Investigating the impact of the genetic variant CXCR1 (rs2234671) in individuals with urinary tract infections.

BACKGROUND: Urinary tract infections (UTIs) are currently posing a worldwide health concern by affecting millions of people. The genetic variant rs2234671 in the CXCR1-interleukin-8 receptor is closely related to a raised UTI risk. OBJECTIVES: In this work, the impact of CXCR1 (rs2234671) on UTI individuals was examined. METHODS: The demographic features of 30 recurrent UTI patients and 20 controls were thoroughly investigated. Bacterial isolation and identification were performed by the implementation of cultural and biochemical methods. DNA extraction, purification of all samples from both patients and healthy people, and IL-8 rs2234671 (C/G) SNP genotyping using T-ARMS-PCR were performed. The significance of the results was evaluated by carrying out a statistical analysis. FINDINGS: The patient's average age was 34.63 ± 11.44 years, and controls averaged 30.30 ± 8.59 years (P= 0.156). No significant gender difference existed (P= 0.804). Escherichia coli (63.3%) was predominant, followed by Proteus mirabilis (26.7%), Enterococcus faecalis (23.3%), Klebsiella pneumoniae (10.0%), and Pseudomonas aeruginosa (20.0%). No significant association was found between bacterial species frequency, age, or sex. From the CXCR1 (rs2234671) frequency comparison, a higher GG genotype incidence in UTI patients than controls was extracted (26.7% vs. 15.0%), though not statistically significant. Risk analysis revealed that GG homozygous and C/G heterozygous genotypes were not UTI risk factors (OR = 2.47 and OR = 1.85, respectively). Moreover, the allele frequencies displayed no significant difference between the patients and controls (G allele: 66.7% vs. 66.7%; C allele: 33.3% vs. 33.3%). MAIN CONCLUSIONS: Although no significant association between CXCR1 (rs2234671) and UTI was found, the GG genotype may point to the increasing probability of UTI risk. Additional research is required to confirm and expand these conclusions.

Performance of a 74-Microhaplotype Assay in Kinship Analyses.

Microhaplotypes (MHs) consisting of multiple SNPs and indels on short stretches of DNA are new and interesting loci for forensic genetic investigations. In this study, we analysed 74 previously defined MHs in two of the populations that our laboratory provides with forensic genetic services, Danes and Greenlanders. In addition to the 229 SNPs that originally made up the 74 MHs, 66 SNPs and 3 indels were identified in the two populations, and 45 of these variants were included in new definitions of the MHs, whereas 24 SNPs were considered rare and of little value for case work. The average effective number of alleles (Ae) was 3.2, 3.0, and 2.6 in Danes, West Greenlanders, and East Greenlanders, respectively. High levels of linkage disequilibrium were observed in East Greenlanders, which reflects the characteristics of this population that has a small size, and signs of admixture and substructure. Pairwise kinship simulations of full siblings, half-siblings, first cousins, and unrelated individuals were performed using allele frequencies from MHs, STRs and SNPs from Danish and Greenlandic populations. The MH panel outperformed the currently used STR and SNP marker sets and was able to differentiate siblings from unrelated individuals with a 0% false positive rate and a 1.1% false negative rate using an LR threshold of 10,000 in the Danish population. However, the panel was not able to differentiate half-siblings or first cousins from unrelated individuals. The results generated in this study will be used to implement MHs as investigative markers for relationship testing in our laboratory.

Investigation of Recessive Effects of Coding Variants on Common Clinical Phenotypes in Exome-Sequenced UK Biobank Participants.

INTRODUCTION: Previous studies have demonstrated effects of rare coding variants on common, clinically relevant phenotypes although the additive burden of these variants makes only a small contribution to overall trait variance. Although recessive effects of individual homozygous variants have been studied, little work has been done to elucidate the impact of rare coding variants occurring together as compound heterozygotes. METHODS: In this study, attempts were made to identify pairs of variants likely to be occurring as compound heterozygotes using 200,000 exome-sequenced subjects from the UK Biobank. Pairs of variants, which were seen together in the same subject more often than would be expected by chance, were excluded as it was assumed that these might be present in the same haplotype. Attention was restricted to variants with minor allele frequency ≤0.05 and to those predicted to alter amino acid sequence or prevent normal gene expression. For each gene, compound heterozygotes were assigned scores based on the rarity and predicted functional consequences of the constituent variants and the scores were used in a logistic regression analysis to test for association with hypertension, hyperlipidaemia, and type 2 diabetes. RESULTS: No statistically significant associations were observed and the results conformed to the distribution, which would be expected under the null hypothesis. The average number of apparently compound heterozygous subjects for each gene was only 282.2. CONCLUSION: It seems difficult to detect an effect of compound heterozygotes on the risk of these phenotypes. Even if recessive effects from compound heterozygotes do occur, they would only affect a small number of people and overall would not make a substantial contribution to phenotypic variance. This research has been conducted using the UK Biobank Resource.

Relationship between vitamin D receptor genotypes (FOK1rs2228570) and IL18 gene expression in sample of multiple sclerosis Iraqi patients.

BACKGROUND: Multiple Sclerosis known as MS, this chronic inflammatory demyelinating condition affects the nervous system. It is a heterogenic and multifactorial disease. The goal of the current study was to investigate the relationship between MS patients' IL18 gene expression and the vitamin D receptor gene polymorphism (FOK1rs2228570). OBJECTIVE: The aim of the study to investigate the association of vitamin D receptor (FOK1rs2228570) gene polymorphism and pro inflammatory cytokine (IL18) gene expression among multiple sclerosis Iraqi patients. Detection VDR polymorphism and determine whether this SNP is involved in susceptibility to multiple sclerosis and estimation IL18 gene expression and explore its relation with multiple sclerosis susceptibility. METHODS: Blood samples were taken from 75 MS patients in Iraq (30 men and 45 women), as well as from 75 volunteers who seemed to be in a favorable state of health and fell within the age range of 20 to 50 years. Tetra-ARMS Polymerase Chain Reaction (Tetra-ARMS PCR) was used to find polymorphisms in the vitamin D receptor (VDR) gene, and Real-time Polymerase Chain Reaction (RT-PCR) was used to measure IL18 gene expression. RESULTS: The findings from the analysis of VDR gene polymorphism in patients with MS indicated that the wild-type genotype T/T was present in 8 individuals, accounting for 10.6%, the heterogeneous genotype TC was 36 (48%), and the homogeneous genotype CC was 31 (41.3%), whilst T allele frequency was 52(34.6%) and C allele was 98(65.3%) with (P⩽ 0.01) significant difference and even as in control T/T genotype was 49(65.3%), TC genotype was 21(28%), CC genotype was 5(6.66%), T allele frequency was 119(79.3%) and C allele was 31(20.6%) with significant difference (P⩽ 0.001). While estimation of IL18 expression showed high elevation in patients' group (2.59 ± 0.51 fold) by significance difference (P⩽ 0.5) when compared to control group (1.35 ± 0.14 fold). The relationship between IL18 gene expression with VDR variant in MS patients demonstrated a significant rise (2.9 ± 0.51 fold) at CC genotype patients in IL18 folding gene expression, followed by (4.6 ± 0.17 fold) in TC genotype patients and finally (1.4 ± 0.08 fold) in TT genotype patients with highly significant (P⩽ 0.01). CONCLUSION: The VDR(FOK1rs2228570) genotype was significantly correlated with IL18 expression in MS patients from Iraq.

A gene pathogenicity tool "GenePy" identifies missed biallelic diagnoses in the 100,000 Genomes Project.

PURPOSE: The 100,000 Genomes Project diagnosed a quarter of affected participants, but 26% of diagnoses were not on the applied gene panel(s); with many being de novo variants. Assessing biallelic variants without a gene panel is more challenging. METHODS: We sought to identify missed biallelic diagnoses using GenePy, which incorporates allele frequency, zygosity, and a user-defined deleterious metric, generating an aggregate GenePy score per gene, per participant. We calculated GenePy scores for 2862 recessive disease genes in 78,216 100,000 Genomes Project participants. For each gene, we ranked participant GenePy scores and scrutinized affected participants without a diagnosis, whose scores ranked among the top 5 for each gene. In cases which participant phenotypes overlapped with the disease gene of interest, we extracted rare variants and applied phase, ClinVar, and ACMG classification. RESULTS: 3184 affected individuals without a molecular diagnosis had a top-5-ranked GenePy score and 682 of 3184 (21%) had phenotypes overlapping with a top-ranking gene. In 122 of 669 (18%) phenotype-matched cases (excluding 13 withdrawn participants), we identified a putative missed diagnosis (2.2% of all undiagnosed participants). A further 334 of 669 (50%) cases have a possible missed diagnosis but require functional validation. CONCLUSION: Applying GenePy at scale has identified 456 potential diagnoses, demonstrating the value of novel diagnostic strategies.

Psychiatric Level 1A evidence pharmacogenomics in a Brazilian admixed cohort and global populations.

Purpose: To compare minor allele frequencies (MAFs) of psychiatric drug response variants in a Brazilian admixed cohort with global populations and other Brazilian groups. Methods: PharmGKB MAFs were gathered from publicly available genetic datasets for Brazil and worldwide. Results: Among 146 variants in CYP2D6 and CYP2C19, 41 were present in Brazil, mostly rare (MAF <1%). 11 variants showed significant MAF differences with large effect sizes compared with global populations. CYP2C19*3 (rs4986893), CYP2C19*17 (rs12248560), CYP2D6*17 (rs28371706-A) and CYP2D6*29 (rs61736512) exhibited higher frequencies in Brazil, with the latter three also differing from other Brazilian groups. Conclusion: This study highlights significant pharmacogenomic diversity in Brazil and globally, underscoring the need for more research in personalized psychiatric drug therapy.

Joint Linkage and Association Analysis Using GENEHUNTER-MODSCORE with an Application to Familial Pancreatic Cancer.

INTRODUCTION: Joint linkage and association (JLA) analysis combines two disease gene mapping strategies: linkage information contained in families and association information contained in populations. Such a JLA analysis can increase mapping power, especially when the evidence for both linkage and association is low to moderate. Similarly, an association analysis based on haplotypes instead of single markers can increase mapping power when the association pattern is complex. METHODS: In this paper, we present an extension to the GENEHUNTER-MODSCORE software package that enables a JLA analysis based on haplotypes and uses information from arbitrary pedigree types and unrelated individuals. Our new JLA method is an extension of the MOD score approach for linkage analysis, which allows the estimation of trait-model and linkage disequilibrium (LD) parameters, i.e., penetrance, disease-allele frequency, and haplotype frequencies. LD is modeled between alleles at a single diallelic disease locus and up to three diallelic test markers. Linkage information is contributed by additional multi-allelic flanking markers. We investigated the statistical properties of our JLA implementation using extensive simulations, and we compared our approach to another commonly used single-marker JLA test. To demonstrate the applicability of our new method in practice, we analyzed pedigree data from the German National Case Collection for Familial Pancreatic Cancer (FaPaCa). RESULTS: Based on the simulated data, we demonstrated the validity of our JLA-MOD score analysis implementation and identified scenarios in which haplotype-based tests outperformed the single-marker test. The estimated trait-model and LD parameters were in good accordance with the simulated values. Our method outperformed another commonly used JLA single-marker test when the LD pattern was complex. The exploratory analysis of the FaPaCa families led to the identification of a promising genetic region on chromosome 22q13.33, which can serve as a starting point for future mutation analysis and molecular research in pancreatic cancer. CONCLUSION: Our newly proposed JLA-MOD score method proves to be a valuable gene mapping and characterization tool, especially when either linkage or association information alone provide insufficient power to identify the disease-causing genetic variants.

The role of HLA genetic variants in COVID-19 susceptibility, severity, and mortality: A global review.

BACKGROUND: The COVID-19 pandemic has had a profound global impact, with variations in susceptibility, severity, and mortality rates across different regions. While many factors can contribute to the spread and impact of the disease, specifically human leukocyte antigen (HLA) genetic variants have emerged as potential contributors to COVID-19 outcomes. METHODS: In this comprehensive narrative review, we conducted a thorough literature search to identify relevant studies investigating the association between HLA genetic variants and COVID-19 outcomes. Additionally, we analyzed allelic frequency data from diverse populations to assess differences in COVID-19 incidence and severity. RESULTS: Our review provides insights into the immunological mechanisms involving HLA-mediated responses to COVID-19 and highlights potential research directions and therapeutic interventions. We found evidence suggesting that certain HLA alleles, such as HLA-A02, may confer a lower risk of COVID-19, while others, like HLA-C04, may increase the risk of severe symptoms and mortality. Furthermore, our analysis of allele frequency distributions revealed significant variations among different populations. CONCLUSION: Considering host genetic variations, particularly HLA genetic variants, is crucial for understanding COVID-19 susceptibility and severity. These findings have implications for personalized treatment and interventions based on an individual's genetic profile. However, further research is needed to unravel the precise mechanisms underlying the observed associations and explore the potential for targeted therapies or preventive measures based on HLA genetic variants.

Comprehensive whole-genome analyses of the UK Biobank reveal significant sex differences in both genotype missingness and allele frequency on the X chromosome.

The UK Biobank is the most used dataset for genome-wide association studies (GWAS). GWAS of sex, essentially sex differences in minor allele frequencies (sdMAF), has identified autosomal SNPs with significant sdMAF, including in the UK Biobank, but the X chromosome was excluded. Our recent report identified multiple regions on the X chromosome with significant sdMAF, using short-read sequencing of other datasets. We performed a whole genome sdMAF analysis, with ~410 k white British individuals from the UK Biobank, using array genotyped, imputed or exome sequencing data. We observed marked sdMAF on the X chromosome, particularly at the boundaries between the pseudo-autosomal regions (PAR) and the non-PAR (NPR), as well as throughout the NPR, consistent with our earlier report. A small fraction of autosomal SNPs also showed significant sdMAF. Using the centrally imputed data, which relied mostly on low-coverage whole genome sequence, resulted in 2.1% of NPR SNPs with significant sdMAF. The whole exome sequencing also displays sdMAF on the X chromosome, including some NPR SNPs with heterozygous genotype calls in males. Genotyping, sequencing and imputation of X chromosomal SNPs requires further attention to ensure the integrity for downstream association analysis.

Analysis of IL-1ß, TGF-ß, IL-5, ACE, PTPN22 gene polymorphisms, and gene expression levels in Turkish children with IgA vasculitis.

OBJECTIVE: Immunoglobulin-A vasculitis (IgAV) is an inflammatory disease that affects small blood vessels. This study was performed to identify an association between protein tyrosine phosphatase non-receptor type 22 (PTPN22) + 788G > A (rs33996649), transforming growth factor-beta (TGF-ß) -509C > T (rs18004069), interleukin 1-beta (IL-1ß) -511C > T (rs16944), interleukin 5 (IL-5) -746C/T (rs2069812), and angiotensin-converting enzyme (ACE) I/D (rs4646994) gene polymorphisms, susceptibility to IgAV, as well as the mRNA levels of IL-1ß, IL-1ß, and TGF-ß. METHOD: A total of 53 patients with IgAV and 50 healthy controls were enrolled. PTPN22, TGF-ß, IL-1ß, ACE gene polymorphisms, ACE gene I/D polymorphisms, and mRNA expression levels were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, allele-specific PCR, and real-time PCR with TaqMan kits, respectively. RESULTS: PTPN22, TGF-ß, IL-1ß, IL-5, and ACE variants showed no genotype or allele differences between patients with IgAV and controls. Increased levels of IL-1ß and TGF-ß mRNA expressions were observed in patients with IgAV (p < 0.001). Patients with the IL-1ß AG genotype showed significantly increased amounts of arthritis than patients with non-AG (p = 0.004). Age at disease onset was found to be significantly different in patients with IgAV according to the presence of TGF-ß TT genotype (p = 0.047). CONCLUSION: Polymorphisms in PTPN22, TGF-ß, IL-5, IL-1ß, and ACE genes are unlikely to confer susceptibility to IgAV. However, the presence of the AG genotype of IL-1ß is associated with susceptibility to IgAV-related arthritis. This is the first study to report a significant increase in serum mRNA levels of IL-1ß and TGF-ß in IgAV patients, supporting a susceptibility to IgAV in childhood.

A novel intergenic variant, rs2004339 A/G, of the gene encoding interleukin-40, C17orf99, is associated with risk of rheumatoid arthritis in Iraqi women.

Interleukin-40 (IL-40) is a novel cytokine encoded by the chromosome 17 open reading frame 99 (C17orf99) gene. Recent studies have shown that IL-40 levels are significantly up-regulated in patients with rheumatoid arthritis (RA). However, the association of genetic variants of the C17orf99 gene with the risk of RA has not been investigated. In this case-control study, two intergenic variants, rs2004339 A/G and rs2310998 G/A, were genotyped for the first time in 120 Iraqi women with RA (30 newly diagnosed [ND] and 90 medicated [MD; treated with the tumor necrosis inhibitor etanercept plus methotrexate]) and 110 control women using TaqMan 5'-allele discrimination method. Serum IL-40 levels were also determined using an enzyme-linked immunosorbent assay kit. Multinomial logistic regression analysis was used to analyze rs2004339 and rs2310998 under five genetic models (allele, recessive, dominant, over-dominant, and co-dominant). Results revealed that the mutant A allele (allele model) and the homozygous AA genotype (co-dominant model) of rs2004339 were significantly associated with an increased risk of RA (odds ratio [OR] = 3.37 and 7.44, respectively; corrected probability [pc] < 0.001), while rs2310998 showed no association with RA risk. When comparing the allele and genotype frequencies of rs2004339 and rs2310998 between ND and MD patients, there were no statistically significant differences. Haplotype analysis of the two variants (in the order rs2004339-rs2310998) revealed that haplotypes A-A (OR = 1.72; pc = 0.024) and A-G (OR = 2.85; pc < 0.001) were associated with an increased risk of RA. IL-40 levels (median and interquartile range) were significantly elevated in RA patients compared to controls (29.3 [15.5-41.5] vs. 12.6 [7.4-18.8] pg/mL; p < 0.001). IL-40 levels were not influence by disease duration or disease activity, but the rs2310998 genotypes had an effect; IL-40 levels were significantly higher in women with the AA genotype than in women with the GG genotype (20.1 [12.9-37.1] vs. 15.8 [8.3-22.6] pg/mL; p = 0.006). Regarding medication, IL-40 tended to show elevated levels in ND cases compared to MD cases but without a significant difference. In conclusion, the mutant A allele and the mutant-type AA genotype of the intergenic variant rs2004339 were associated with an increased risk of RA among Iraqi women. Serum IL-40 levels were also elevated in patients, particularly ND patients, and were positively affected by the mutant-type AA genotype. Accordingly, the role of IL-40 in the pathogenesis of RA has been indicated.

Genetic preservation of SLC22A3 in the Admixed and Xhosa populations living in the Western Cape.

BACKGROUND: Amphiphilic solute facilitator organic cation transporters mediate the movement of various endogenous and exogenous organic cations, including crucial drugs like metformin, oxaliplatin, and lamivudine. These transporters are now seen as a potential explanation for inter-individual differences in drug effectiveness, contributing to 15-30% of such variability due to genetic factors.The aim of this study was to determine the baseline minor allele frequency distribution of 18 known coding SNPs in the SLC22A3 gene of 278 Cape Admixed (130) and Xhosa (148) individuals residing in Cape Town, South Africa. METHODS: A convenience sampling method was used for sample collection. DNA extraction and subsequent amplification of target sites was carried out according to standard established methodologies. All genotyping was performed using the SNaPshot™ mini-seuqencing platform. RESULTS: This study found no genetic polymorphisms in the coding region of the SLC22A3 gene of both the Xhosa and Cape Admixed individuals investigated. CONCLUSION: This study has shown that SLC22A3 coding SNPs observed in other populations are absent in the sample of both Cape Admixed and Xhosa individuals studied. The lack of protein sequence variation was consistent with other studies and may reflect the significant physiological role of human organic cation transporter 3 in maintaining cellular and organismal homeostasis.