Adverse effect of VEGFR-2 (rs1870377) polymorphism on the clinical course of COVID-19 in females and males in an age-dependent manner.

The COVID-19 pandemic has affected people worldwide with varying clinical presentations ranging from mild to severe or fatal, and studies have found that age, gender, and some comorbidities can influence the severity of the disease. It would be valuable to have genetic markers that might help predict the likely outcome of infection. For this objective, genes encoding VEGFR-2 (rs1870377), CCR5Δ32 (rs333), and TLR3 (rs5743313) were analyzed for polymorphisms in the peripheral blood of 160 COVID-19 patients before COVID-19 vaccine was available in Türkiye. We observed that possession of the VEGFR-2 rs1870377 mutant allele increased the risk of severe/moderate disease in females and subjects ≥65 years of age, but was protective in males <65 years of age. Other significant results were that the CCR5Δ32 allele was protective against severe disease in subjects ≥65 years of age, while TLR3 rs5743313 polymorphism was found to be protective against severe/moderate illness in males <65 years of age. The VEGFR-2 rs1870377 mutant allele was a risk factor for severe/moderate disease, particularly in females over the age of 65. These findings suggest that genetic polymorphisms have an age- and sex-dependent influence on the severity of COVID-19, and the VEGFR-2 rs1870377 mutant allele could be a potential predictor of disease severity.

Do CCR5 (CCR5Δ32) and TLR3 (RS5743313) gene polymorphisms prevent chronic hepatitis B infection?

Hepatitis B virus (HBV) is still a significant health problem in human. HBV severity or sensitivity of patients may be based on the individual genetic factors significantly. The aim of this study is to investigate the association of CCR5 (CCR5Δ32), TLR3 (rs5743313) functional gene polymorphisms, interferon-gamma (IFN-É£) level in HBV infection, which are thought to play an important role in innate and acquired immunity in patients who have undergone HBV seroconversion and those who have chronic hepatitis B disease and receive treatment. One hundred patients who are became naturally immune against HBV infection (HBsAg negative, anti-HBc IgG, and anti-HBs IgG positive), and 100 patients with chronic hepatitis B infection (>6 months HBsAg positive) who are receiving oral antiviral therapy were compared for CCR5Δ32, TLR3 (rs5743313) genotypes and serum IFN-É£ level. It was found that CCR5Δ32 polymorphism (Wt/Δ32 and Δ32/Δ32) was significantly higher in the chronic hepatitis B group (p = 0.048) but not for TLR3 gene polymorphism. However, serum IFN-É£ level was significantly higher in the HBV seroconversion group (75 ± 89 ng/ml) than in the chronic hepatitis B group (4.35 ± 17.27 ng/ml) (p < 0.001). In conclusion, a higher CCR5Δ32 allele frequency in patients with chronic hepatitis B might be considered as a marker of progression to chronic hepatitis.

A Case Report of a Prenatally Missed Mowat-Wilson Syndrome With Isolated Corpus Callosum Agenesis.

Mowat-Wilson syndrome (MWS) is an autosomal dominant genetic disorder caused by ZEB2 gene mutations, manifesting with unique facial characteristics, moderate to severe intellectual problems, and congenital malformations as Hirschsprung disease, genital and ophthalmological anomalies, and congenital cardiac anomalies. Herein, a case of 1-year-old boy with isolated agenesis of corpus callosum (IACC) in the prenatal period is presented. He was admitted postnatally with Hirschsprung disease (HSCR), hypertelorism, uplifted earlobes, deeply set eyes, frontal bossing, oval-shaped nasal tip, ''M'' shaped upper lip, opened mouth and prominent chin, and developmental delay. Hence, MWS was primarily considered and confirmed by the ZEB2 gene mutation analysis. His karyotype was normal. He had a history of having a prenatally terminated brother with similar features. Antenatally detected IACC should prompt a detailed investigation including karyotype and microarray; even if they are normal then whole exome sequencing (WES) should be done.

The association of paraoxonase 1 gene L55M polymorphism with the extent and severity of coronary artery disease in the Turkish population and its dependence on gender.

OBJECTIVE: Coronary artery disease (CAD) is a common, complex, and progressive disorder characterized by the accumulation of lipids and fibrous elements in the arteries. It is one of the leading causes of death in industrialized nations. Oxidative modification of low-density lipoprotein (LDL) in the arterial wall plays an important role in the initiation and progression of atherosclerosis. Paraoxonase1 (PON1) is involved in lipid metabolism and is believed to protect LDL oxidation. In our study, we aimed to clarify the relationship between PON1 gene L55M polymorphism and the extent and severity of CAD. METHODS: In total, 114 patients (54 males, mean age: 56.7 ± 12.0 years; 60 females, mean age: 55.7 ± 13.2 years) with stable angina or angina equivalent symptoms were enrolled in this prospective study. Cardiological evaluation was performed with electrocardiogram and transthoracic echocardiogram. The presence of hypertension, dyslipidemia, diabetes, and smoking status were ascertained. The patients were grouped according to their Gensini scores and gender. Genetic analysis of the PON1 gene L55M polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: We determined that the LL genotype was more prevalent in patients with Gensini score higher than or equal to 20 (p=0.026) and that this correlated with severe atherosclerotic coronary artery lesions in both gender groups, reaching a statistical significance in the female subjects (p=0.038). CONCLUSION: It was thought that the PON1 gene L55M polymorphism plays a significant role in CAD progression, especially in females.

The frequency of Familial Mediterranean fever gene mutations and genotypes at Kirikkale and comparison with the mean of regional MEFV mutation frequency of Turkey.

In this study we have retrospectively analysed the mutation spectrum of the 351 Familial Mediterranean fever patients referred to Kirikkale University Faculty of Medicine, Department of Medical Genetics Laboratory over a period of 5 years and compared them with Turkey's mean. We have found 11 different mutations, including rare mutations such as F479L, K695R, M680I(G/A) and 45 different genotypes showing the heterogeneity of MEFV mutations in Central Anatolia. The most three prevalent mutations were M694V (14.8%), E148Q (7.1%) and M680I(G/C) (4.1%) in accordance with the literature. We have also investigated R202Q in our routine molecular diagnosis. Mutation causing R202Q (c.605G > A) change was described as a frequent polymorphism and G allele was found in linkage disequilibrium (LD) with M694V. There are limited number of studies investigating R202Q, some of them implicate that its homozygote state is disease causing. We showed the high frequency of R202Q (23.7%) with and without M694V in all the groups analysed and its high LD rate with M694V in the diagnosed group. Our study is reflecting the mutational heterogeneity of MEFV and summarize mutational spectrum of Turkey's geographical regions and overall Turkey.