Analysis of ACE2 and TMPRSS2 coding variants as a risk factor for SARS-CoV-2 from 946 whole-exome sequencing data in the Turkish population.

Heterogeneity in symptoms associated with COVID-19 in infected patients remains unclear. ACE2 and TMPRSS2 gene variants are considered possible risk factors for COVID-19. In this study, a retrospective comparative genome analysis of the ACE2 and TMPRSS2 variants from 946 whole-exome sequencing data was conducted. Allele frequencies of all variants were calculated and filtered to remove variants with allele frequencies lower than 0.003 and to prioritize functional coding variants. The majority of detected variants were intronic, only two ACE2 and three TMPRSS2 nonsynonymous variants were detected in the analyzed cohort. The main ACE2 variants that putatively have a protective or susceptibility effect on SARS-CoV-2 have not yet been determined in the Turkish population. The Turkish genetic makeup likely lacks any ACE2 variant that increases susceptibility to SARS-CoV-2 infection. TMPRSS2 rs75603675 and rs12329760 variants that were previously defined as common variants that have different allele frequencies among populations and may have a role in SARS-CoV-2 attachment to host cells were determined in the population. Overall, these data will contribute to the formation of a national variation database and may also contribute to further studies of ACE2 and TMPRSS2 in the Turkish population and differences in SARS-CoV-2 infection among other populations.

Increased Plasma Levels of Asymmetric Dimethylarginine in Nonalcoholic Fatty Liver Disease: Relation With Insulin Resistance, Inflammation, and Liver Histology.

BACKGROUND AND AIM: Cardiovascular disease (CVD) is the most frequent cause of death in nonalcoholic fatty liver disease (NAFLD). Insulin resistance, hepatic dysfunction, and chronic inflammation are factors interacting in explaining the increased CVD incidence in NAFLD. We aimed to evaluate the effects of insulin resistance and inflammatory biomarkers on asymmetric dimethylarginine (ADMA) levels, a predictor of CVD. We also investigated relationship between these markers and histological findings in patients with NAFLD. PATIENTS AND METHODS: Plasma ADMA, high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), and homeostasis model assessment of insulin resistance (HOMA-IR) were measured in 70 patients with histologically verified NAFLD (53 with nonalcoholic steatohepatitis [NASH], 17 with non-NASH) and 12 controls. RESULTS: The HOMA-IR (5.3 [3.9] vs 1.9 [1], P < 0.001), hs-CRP (5.6 [4.2] vs 2.2 [2.3] mg/L, P < 0.001), ADMA (0.81 [0.25] vs 0.48 [0.24] µmol/L, P = 0.005), and IL-6 (4.1 [1.2] vs 1.0 [0.4] pg/mL, P < 0.001) levels were all found higher in the NAFLD group than the control group. The ADMA levels were significantly higher in patients with NAFLD independent from HOMA-IR and body composition (P = 0.02). The IL-6 and HOMA-IR levels of the NASH group were found significantly higher than those of the non-NASH group. The only determinant significantly correlated to ADMA was HOMA-IR. CONCLUSIONS: Our data suggested that although ADMA levels are independently higher in NAFLD, the only determinant correlated to ADMA is HOMA-IR and not inflammatory biomarkers (hs-CRP, IL-6) or presence/absence of NASH.

Comparison of apoptotic gene expression profiles between Peyronie's disease plaque and tunica albuginea.

BACKGROUND: The fibrotic plaques of Peyronie/s disease and other localized fibrotic conditions have been considered to be the result of an abnormal wound healing process. The potential role of regulatory disorders of apoptosis in abnormal wound healing may also play a role in the development of Peyronie's disease. OBJECTIVES: To examine the phenomenon of apoptosis in Peyronie's disease, authors quantified differential levels of gene expression of apoptotic proteins, Fas, Fas Ligand, Bcl-2, p53, Caspase 3 and 8 in Peyronie's plaque and tunica albuginea. MATERIAL AND METHODS: Eight patients with Peyronie's disease undergoing surgical correction of the curvature had biopsy specimens taken from both the Peyronie's plaque and normal tunica albuginea. Messenger RNA expression of the apoptotic proteins in the plaque and normal tunica was measured by reverse transcriptase PCR. RESULTS: Apoptotic gene expression was lower than the housekeeping gene's in half of the tunica albuginea samples and two thirds of the plaque samples. Overall mRNA expressions in the plaque were not significantly different from the normal tunica albuginea. CONCLUSIONS: The fibrotic plaques of Peyronie's disease and other localized fibrotic conditions have been considered to be the result of an abnormal wound healing process. The potential role of regulatory disorders of apoptosis in abnormal wound healing may also play a role in the development of Peyronie's disease. In this study, the lower expression of apoptotic genes may cause the persistence of collagen producing cells which were up-regulated for unknown reasons and consequently result in plaque formation. Similar expression levels of apoptotic genes in both tunica albuginea and Peyronie's plaques may be due to the generalized physiopathologic alterations in tunica albuginea that lead to plaque formation at a vulnerable region subjected to recurrent traumas.

Association of MDR1 (C3435T) polymorphism and resistance to carbamazepine in epileptic patients from Turkey.

BACKGROUND AND AIMS: We investigated the prevalence of this multidrug resistance 1 gene (MDR1) polymorphism in drug-responsive versus drug-resistant epilepsy patients treated with carbamazepine (CBZ), which is a substrate of this protein. METHODS: We genotyped the C3435T variant of MDR1 in 97 patients treated with CBZ monotherapy who had been on stable doses for more than 1 month. Our control group included 174 healthy individuals. Plasma CBZ concentrations were also measured using fluorescence polarization immunoassay. RESULTS: We could not demonstrate any statistically significant relationship with the genotypes among drug-resistant patients (n = 44). The frequency of the homozygous mutant (TT) genotype was 15% in drug-responsive patients, 11.3% in drug-resistant patients and 25.8% in the control group. We also did not observe any significant correlation between the presence of a specific allele and CBZ plasma level/dose index. CONCLUSION: Our study did not support any significant association between the MDR1 (C3435T) polymorphism and resistance to CBZ in epilepsy patients from Turkey.