OBJECTIVE: A wide range of clinical manifestations and outcomes, including liver injury, have been reported in COVID-19 patients. We investigated the association of three substantial gene polymorphisms (FURIN, IFNL4, and TLR2) with COVID-19 disease susceptibility and severity to help predict prognosis.
METHODS: 150 adult COVID-19-assured cases were categorized as follows: 78 patients with a non-severe presentation, 39 patients with severe disease, and 33 critically ill patients. In addition, 74 healthy controls were included. Clinical and laboratory evaluations were carried out, including complete and differential blood counts, D-dimer, lactate dehydrogenase (LDH), C-reactive protein (CRP), procalcitonin, ferritin, interleukin-6 (Il-6), and liver and kidney functions. FURIN (rs6226), IFNL4 (rs12979860), and TLR2 (rs3804099) genotyping allelic discrimination assays were conducted using real-time PCR.
RESULTS: The FURIN, IFNL4, and TLR2 genotypes and their alleles differed significantly between COVID-19 patients and controls, as well as between patients with severe or critical illness and those with a non-severe presentation. According to a multivariable regression analysis, FURIN (C/T + T/T) and TLR2 (T/C + C/C) mutants were associated with COVID-19 susceptibility, with odds ratios of 3.293 and 2.839, respectively. FURIN C/C and IFNL4 T/T mutants were significantly linked to severe and critical illnesses. Multivariate regression analysis showed that FURIN (G/C + C/C) genotypes and IFNL4 T/T homozygosity were independent risk factors associated with increased mortality.
CONCLUSIONS: FURIN, IFNL4, and TLR2 gene variants are associated with the risk of COVID-19 occurrence as well as increased severity and poor outcomes in Egyptian patients.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder that affects women in their child-bearing age, and is associated with insulin resistance and type 2 diabetes. The etiology of PCOS involves multiple factors including genetic, metabolic and immunological factors. Interleukin - 10 (IL-10), as an anti-inflammatory cytokine, plays a critical role in this regard. We investigated the potential role of IL-10 gene variants in the development of PCOS in Tunisian population.
RESULTS: 115 cases and 120 controls were recruited in the current case control study. Rotterdam consensus criteria were used to diagnose PCOS patients. Genotyping for IL-10, rs1800896, rs1800871 and rs1800872 variants, was performed by real time PCR. The results obtained showed that the minor allele frequency of rs1800896, rs1800871and rs1800872 were comparable between PCOS cases and control subjects (P = 0.30, P = 0.71, and P = 0.57 respectively). The distribution analysis revealed an unsignificant association of the three tested variants, in all genetic models. Haplotype analysis identified one haplotype CCA with a protective role in PCOS development (P = 0.05; OR (95% CI) = 0.56 (0.32 - 0.99)). This association did not persist after adjustment for multiples covariates (Pc = 0.154).
CONCLUSIONS: Our study is the first to show how ethnicity influences the association of IL-10 gene variants with PCOS susceptibility. No allelic nor genetic association were observed between the tested variants and PCOS in Tunisian women, however, a particular IL-10 haplotype with a protective effect for PCOS was identified.

A role for resistin in the pathogenesis of polycystic ovarian syndrome (PCOS) and related features were described for various ethnicities. As its expression is partly inherited, a role for RETN polymorphisms in regulating resistin levels and PCOS risk was shown, but with varied results.
To investigate the association of rs34124816 (-537A>C), rs1862513 (-420C>G), rs3219175 (-358G>A), rs3745367 (+299G>A), rs3745369 (+1263G>C), and rs1423096 (+4965C>T) RETN SNPs with PCOS.
Study subjects included 583 women with PCOS, and 713 eumenorrheic women serving as controls. Genotyping was done by real-time PCR.
Higher minor allele frequency (MAF) of rs34124816, rs3219175, and rs3745369, and lower MAF of rs1862513 and rs1423096 were seen in PCOS cases. Reduced PCOS risk was found with rs3745367 minor-allele homozygotes and rs1423096 minor-allele homozygotes, while increased risk was linked with rs3745367 heterozygotes, and with rs3745369 heterozygotes and minor-allele homozygotes. While it did not reach statistical significance, serum resistin levels were elevated in PCOS cases than in control women and major-allele homozygotes of rs34124816 and rs1862513, and in rs1423096 minor-allele-containing carriers. Carriage of rs34124816 correlated positively with age and LH, whereas rs1862513 positively and rs3745367 negatively correlated with fasting glucose. Six-locus (rs34124816-rs1862513-rs3219175-rs3745367-rs3745369-rs1423096) haplotype analysis demonstrated a significant reduction in AGGGGG and a marked increase in AGGGCG haplotypes between cases and controls, thus assigning PCOS protective and susceptible nature to these haplotypes, respectively.
This study is the first to document the contribution of rs34124816 and rs1423096 RETN variants to the risk of PCOS. The varied association of RETN gene variants with PCOS suggests an ethnic contribution of RETN association with PCOS.

OBJECTIVE: One of the potential factors that cause systemic lupus erythematosus (SLE) development is autophagy. Immunity-related GTPase family M protein (IRGM) has been shown to be linked to immune-mediated diseases. The aim of the current study was to assess the role of the IRGM-autophagy gene in SLE susceptibility in an Egyptian population and its relation to lupus nephritis.
METHODS: A case-control study was conducted in which a total of 200 subjects (100SLE and 100 healthy controls) were enrolled. Two single-nucleotide polymorphisms (SNPs) (rs10065172 and rs4958847) were genotyped. Genotypes and alleles analysis was conducted to compare between cases and controls, as well as a stratification analysis was conducted on the presence or absence of lupus nephritis.
RESULTS: Among selected SNPs of IRGM, no association was found between both SNPs and SLE susceptibility. For rs10065172, the major expressed genotype was CC (61% and 71%) (Adj OR= 2.9, 95%= 0.545-15.5), followed by TC (34% and 27%) (Adj OR= 1.985, 95% = 0.357-11.041) in cases and controls, respectively. For rs4958847, AA and AG were comparably expressed in case [(43% and 39%) (Adj OR= 1.073, 95% = 0.483-2.382)] and control [(41% and 43%) (Adj OR= 1.24, 95% = 0.557- 2.763)], respectively. Additionally, no relationship among both SNPs and gender, lupus nephritis, disease activity, or disease duration, was observed.
CONCLUSIONS: IRGM SNPs (rs10065172 and rs4958847) expression was comparable among SLE patients and controls of the Egyptian cohort. Genotype and allele frequency of IRGM SNPs did not differ in lupus nephritis and non-lupus nephritis patients.

Prenatal imaging phenotypes and genotypes were analyzed in 13 cases prenatally diagnosed with Joubert syndrome (JS), all of which underwent magnetic resonance imaging (MRI), ultrasound, and genetic testing. Prenatal MRI diagnosed 10 cases as JS with a typical molar tooth sign (MTS), while prenatal ultrasound diagnosed or suspiciously diagnosed 11 cases as JS with typical or mild MTS in 10 cases. Mutations in JS-related genes and other prenatal JS imaging phenotypes were identified in 10 cases, including OFD1 in two cases [cerebellar vermis (CV) absence, posterior fossa dilation, ventriculomegaly, polydactyly, malformations of cortical development (MCD), and persistent left superior vena cava], TMEM67 in two cases (CV absence, polydactyly, hyperechoic kidneys or polycystic kidneys, posterior fossa dilation, and ventriculomegaly), CC2D2A in two cases (CV absence, polydactyly, MCD, agenesis of the corpus callosum, encephalocele and hydrocephalus, ventriculomegaly, and posterior fossa dilation), RPGRIP1L in one case (CV absence), TCTN3 in one case (CV absence, polydactyly, MCD, and posterior fossa dilation), CEP290 in one case (CV absence and polycystic kidney), and NPHP1 in one case (CV absence). The prenatal diagnosis of JS presents a number of challenges, including the variants of unknown significance, the lack of functional assessment in prenatal imaging, unclear phenotype-genotype relationships in prenatal evaluation, and the incorrect identification of the JS hallmark, the MTS, in prenatal imaging, especially on ultrasound. Although combined MRI, ultrasound, and exome sequencing could help improve the prenatal diagnosis of JS, there still exist significant challenges.

BACKGROUND: We previously reported on the association between ESR1 and ESR2 gene variants and heightened risk of breast cancer (BC). Here we investigated the association of common ESR1 and ESR2 gene variants with triple negative BC (TNBC).
METHODS: This retrospective case-control study involved 488 BC patients (130 TNBC, 358 non-TNBC patients). ESR1 (rs2234693, rs9340799, rs3020314, rs3798577) and ESR2 (rs928554, rs944459, rs4986938, rs1256049, rs1256030, rs1271572) genotyping was done by real-time PCR.
RESULTS: While minor allele frequencies (MAF) of ESR1 variants were comparable between TNBC and non-TNBC subjects, significantly higher ESR2 rs1256049 MAF was seen in TNBC patients. Significantly higher frequency of ESR1 rs3798577 T/C and C/C genotypes were noted in TNBC cases, and significant differences were seen in ESR2 rs928554, rs1256049, and rs1271572 genotype distribution. Increased TNBC risk was associated with ESR1 rs3798577 T/C and C/C genotypes according to codominant and dominant models, while positive association of ESR2 rs928554 with TNBC was seen according to codominant and recessive models, and positive association of ESR2 rs1256049 with TNBC was seen according to codominant and dominant models. Positive interactions were noted between ESR2 rs1271572-ESR1 rs3020314, ESR2 rs1271572-ESR1 rs9340799, and ESR2 rs1271572-ESR1 rs2234693, ESR2 rs4986938-ESR1 rs2234693, and ESR2 rs928554-ESR1 rs9340799. Haplotype analysis confirmed the positive association of ESR1 CATT with TNBC, while ACGGCTC and ACGGTT ESR2 haplotypes were positively associated with TNBC.
CONCLUSIONS: Results of this study confirmed the association of unique ESR1 and ESR2 genetic variants with altered risk of TNBC. This suggests possible diagnostic and prognostic role of these variants with TNBC independent of their association with BC.

OBJECTIVE: What role do ADIPOQ variants play in controlling adiponectin concentrations and altered risk of polycystic ovary syndrome (PCOS)?
METHODS: Study subjects comprised 583 women with PCOS and 713 age-matched controls. Genotyping of rs182052, rs822393, rs822396, rs7649121, rs3774271, rs266729, rs3774261 and rs6773957 ADIPOQ polymorphisms was done by real-time polymerase chain reaction (PCR).
RESULTS: Of the 16 ADIPOQ variants, the minor allele frequencies of rs182052, rs822393, rs822396, rs7649121, rs3774261 and rs6773957 were significantly different between PCOS cases and controls. Significant differences in rs266729 (P = 0.02), rs822396 (P = 0.02), rs3774261 (P < 0.001) and rs6773957 (P < 0.001) genotypes were also noted between PCOS cases and controls. Reduced PCOS risk was found with heterozygous rs266729, while increased risk was linked to heterozygous rs822396 and homozygous minor allele rs3774361, and in heterozygous and homozygous minor allele rs6773957 genotype carriers. Haplotype analysis identified two blocks based on linkage disequilibrium pattern; alleles coded as \'1\' (major) and \'2\' (minor). Within Block 1 (rs4632532, rs16861194, rs266729, rs182052, rs16861209, rs822393, rs822395, rs822396, rs7649121), haplotypes 111111111 and 212211221 were positively, while haplotypes 212212112 and 212211211 were negatively associated with PCOS. Within Block 2 (rs2241766, rs1501299, rs2241767, rs3774261, rs6773957, rs1063539) haplotypes 111221 and 112221 were positively, while haplotype 111111 was negatively associated with PCOS.
CONCLUSIONS: This is the first study to confirm the association of rs182052, rs822393, rs7649121 and rs6773957 ADIPOQ variants with altered risk of PCOS. The varied association of ADIPOQ variants with PCOS in relation to earlier reports indicate there is an ethnic contribution to ADIPOQ association with PCOS.

BACKGROUND: The occurrence of granulomatous amoebic encephalitis (GAE) was investigated due to the exposure of a large number of immunocompromised patients to opportunistic Acanthamoeba infections, which in most cases are fatal.
METHODS: In this case-control study, 160 samples from the nasal mucosa of immunocompromised patients were collected between February 2019 to February 2020 in Isfahan, central Iran, using sterile cotton swabs; 150 ethnically matched controls were included. The pathogenic potential of the identified isolates was evaluated using temperature and osmotolerance assays. The identification of Acanthamoeba infection was confirmed by both morphological and phylomolecular tools.
RESULTS: Of 310 collected samples, 32 strains, including 25 (15.6%) and 7 (4.6%) isolates, were positive for the Acanthamoeba genus in the patient and control groups, respectively. The topology of the phylogenetic tree indicated that all the Acanthamoeba strains belonged to the T4 genotype. Only five of the isolates genotyped as T4 were positive for potential pathogenic assays. The heterogeneity analysis of 18S ribosomal RNA sequences of Acanthamoeba in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and hepatitis B and C patients revealed significant genetic diversity (haplotype diversity [Hd] 0.511) compared with that of healthy individuals (Hd 0.210).
CONCLUSIONS: The circulation of pathogenic isolates of Acanthamoeba, particularly in HIV/AIDS patients, along with their genetic traits, indicates that clinicians should be more aware of fatal cases of GAE, especially in suspected encephalitis, in Iran and worldwide.

Tenofovir disoproxil fumarate (TDF) is effectively used as the first-line antiviral for chronic hepatitis B virus (HBV) infection in adults and children older than 12 years. To date, no confirmed case of virologic breakthrough (VBT) in a pediatric case has been reported.
Here we describe a case of a 5-year old, asymptomatically infected with HBV infection two months after chemotherapy for precursor B acute lymphoblastic leukemia (ALL). Although the 5-year old male is South African, his family originated from Guinea. At the end of the one-year follow-up, the infection progressed to chronic HBV infection, with a high viral load. At 36 weeks (8 months) post-treatment with lamivudine (LAM), there was a partial virologic response (PVR) and after 61 weeks (14 months), he was switched to TDF rescue monotherapy. Even with TDF treatment, he still experienced VBT and subsequent PVR. The full-length genome of HBV isolated 78 weeks after the switch to rescue TDF monotherapy was sequenced and belonged to genotype E. In addition to the LAM mutations (rtS256G and rtM267L), missense mutations in B-cell, T-cell, HLA class I and II-restricted epitopes emerged, which were to evade and escape host surveillance, leading to delayed viral clearance, persistence and disease progression. Two further events of VBT occurred between weeks 113 and 141 of TDF rescue-therapy. Viral loads and liver enzymes are normalizing progressively with long-term therapy.
Although the host immune reconstitution may be delayed, prolonged TDF treatment was effective in treating this pediatric case of HBV infection with VBT and PVR.

Concentration of plant secondary metabolites (SMs) show seasonal variations. However, it is still not well understood how these abiotic and biotic factors influence the seasonal variations of SMs. In addition, it is of interest to know if and how SMs are reallocated to the different plant organs, in particular whether SMs are reallocated to the remaining tissues when biomass is lost, e.g., during winter. Here we used Jacobaea vulgaris, Jacobaea aquatica, two F1 and four F2 hybrids that differed in their pyrrolizidine alkaloids (PAs) bouquet as a study system. A series of clones of these genotypes were investigated during their vegetative stage spanning 14 months in a semi-natural environment. We found that the total PA concentration in roots and shoots showed a gradual increase until the spring of the second year, whereafter it dropped substantially in shoots. The variation in PA composition due to seasonal changes was significant but relatively small. Senecionine-like PAs were the dominant PAs in roots, while jacobine-/erucifoline-like PAs were dominant in shoots. The variation of PA concentration was significantly correlated with temperature, day length, and plant age. A correlation analysis showed that PAs were not reallocated when biomass was lost in winter. Overall, our study showed that PA composition of each genotype changed over seasons in a different manner but seasonal variation did not overrule the differences in PA composition among genotypes.