Worldwide distribution of genetic factors related to severity of COVID-19 infection.

Background: Genome-wide association studies of COVID-19 severity have been carried out mostly on European or East Asian populations with small representation of other world regions. Here we explore the worldwide distribution and linkage disequilibrium (LD) patterns of genetic variants previously associated with COVID-19 severity.

Methods: We followed up the results of a large Spanish genome-wide meta-analysis on 26 populations from the 1000 Genomes Project by calculating allele frequencies and LD scores of the nine most significant SNPs.

and Polymorphisms in Early HER2-Positive Breast Cancer Patients: Relationship with Response to Neoadjuvant Anti-HER2 Treatment.

The addition to chemotherapy of anti-HER2 drugs such as trastuzumab or pertuzumab has improved outcomes in HER2-positive breast cancer patients. However, resistance to these drugs in some patients remains a major concern. This study examines the possible association between the response to neoadjuvant anti-HER2 treatment in breast cancer patients and the presence of 28 SNPs in 17 genes involved in different cell processes (, , , , , , , , , , chr6 intergenic region, , , , , , and ).

Amplification and Response to Neoadjuvant Anti-HER2 Treatment in Early HER2-Positive Breast Cancer.

HER2-positive breast cancer (BC) is an aggressive subtype that affects 20-25% of BC patients. For these patients, neoadjuvant therapy is a good option that targets a pathological complete response (pCR) and more breast-conserving surgery. In effect, the outcomes of patients with HER2-positive BC have dramatically improved since the introduction of anti-HER2 antibodies such as trastuzumab (TZ) and/or pertuzumab (PZ) added to chemotherapy.

miR-7, miR-10a and miR-143 Expression May Predict Response to Bevacizumab Plus Chemotherapy in Patients with Metastatic Colorectal Cancer.

Purpose: Bevacizumab is a monoclonal antibody that binds to vascular endothelial growth factor A. It is currently used in combination with chemotherapy to treat metastatic colorectal cancer. This therapy is not equally effective in every patient; in some, mechanisms of resistance arise that remain poorly understood.

Role of Chromodomain-Helicase-DNA-Binding Protein 4 (CHD4) in Breast Cancer.

Chromodomain-helicase-DNA-binding protein 4 (CHD4) is an epigenetic regulator identified as an oncogenic element that may provide a novel therapeutic target for the treatment of breast cancer (BC). CHD4-the core component of the nucleosome remodeling and deacetylase (NuRD) complex-may be mutated in patients with this disease. However, information on mutants that might allow their use as biomarkers of therapeutic success and prognosis is lacking.

Genetic Variants of , , and Linked to Clinical Outcome of Bevacizumab Plus Chemotherapy for Metastatic Colorectal Cancer.

Angiogenesis pathway genes show substantial genetic variability causing inter-individual differences in responses to anti-angiogenic drugs. We examined 20 single nucleotide polymorphisms (SNPs) in 13 of these genes to predict tumour response and clinical outcome measured as progression free survival (PFS) and overall survival (OS) in 57 patients with metastatic colorectal cancer (mCRC) given bevacizumab plus chemotherapy. SNPs were detected (iPLEX® Assay) in genomic DNA extracted from formalin-fixed paraffin-embedded tumour specimens.

Efficacy of bevacizumab-containing chemotherapy in metastatic colorectal cancer and expression: Six case reports.

Background: In metastatic colorectal cancer (mCRC), the anti-vascular endothelial growth factor drug bevacizumab (BVZ) plus chemotherapy significantly improves progression-free survival compared to chemotherapy (CT) alone. This benefit is not, however, observed in all patients. While increased chemokine gene expression promoting angiogenesis has been proposed as a prognostic mCRC biomarker, few studies have examined its relationship with drug efficacy.

Somatic Mutations in and Implications for Current Treatment Paradigms in -Positive Breast Cancer.

In one of every four or five cases of breast cancer, the human epidermal growth factor receptor-2 () gene is overexpressed. These carcinomas are known as HER2-positive. HER2 overexpression is linked to an aggressive phenotype and a lower rate of disease-free and overall survival.

UDP-glucuronosyltransferase genetic variation in North African populations: a comparison with African and European data.

Background: Genetic variation in glucuronosyltransferases (UGT) is crucial in drug metabolism and risk of some diseases.

Aim: To examine genetic variation in UGT in North African populations.

Subjects And Methods: Allele frequencies of SNPs UGT1A4, UGT1A4, UGT2B15, UGT2B15 and UGT2B17 CNV deletion from Morocco, Algeria, Tunisia and Libya were compared to European and Sub-Saharan populations.

Differential expression of PMCA2 mRNA isoforms in a cohort of Spanish patients with breast tumor types.

The present study examined the mRNA expression levels of different isoforms of the plasma membrane calcium ATPase 2 (PMCA2) gene generated by alternative splicing at the first intracellular loop (site A) and C-terminal region (site C) in 85 human breast cancer tumor and 69 adjacent non-tumor tissues. Associations were identified between the expression of PMCA2 splice isoforms and the following clinical variables: Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status, tumor size, staging and histological classification, and lymph node status. Transcripts including splice site A or splice site C were amplified by reverse transcription-quantitative polymerase chain reaction using PMCA2 isoform-specific primers.

Cytochrome and sulfotransferase gene variation in north African populations.

Aim: To describe the diversity of four cytochrome and four sulfotransferase polymorphisms in six north African samples. Scarce data have been compiled for these samples despite the rich genetic background of north African populations.

Materials & Methods: CYP3A4*1B, CYP3A4*17, CYP3A4*3, CYP3A5*3, SULT1A1*2, SULT1A2*2, SULT1A2*3 and SULT1E1*2 polymorphisms were explored in 556 individuals from Morocco, Algeria, Tunisia and Libya.

Impacts of the Glucuronidase Genotypes UGT1A4, UGT2B7, UGT2B15 and UGT2B17 on Tamoxifen Metabolism in Breast Cancer Patients.

Tamoxifen is used to prevent and treat estrogen-dependent breast cancer. It is described as a prodrug since most of its antiestrogen effects are exerted through its hydroxylated metabolites 4-OH-tamoxifen and endoxifen. In prior work, we correlated optimal plasma levels of these metabolites with certain genotypes of CYP2D6 and SULT1A2.

Genetic diversity of CYP3A4 and CYP3A5 polymorphisms in North African populations from Morocco and Tunisia.

The genes CYP3A4 and CYP3A5 form part of a cluster of cytochrome P450 genes involved in drug metabolism reactions. The allelic variants of these genes CYP3A4*1B, CYP3A4*3, CYP3A4*17 and CYP3A5*3 have been linked both to the reduced catalytic activity of cytochromes and to prostate cancer risk in whites, though scarce data exist for North African populations. The main objective of this study was to describe CYP3A4*3, CYP3A4*17, CYP3A4*1B and CYP3A5*3 allele frequencies and haplotype variation in Moroccan Berbers and the general Tunisian population.

Relationship between genotypes Sult1a2 and Cyp2d6 and tamoxifen metabolism in breast cancer patients.

Tamoxifen is a pro-drug widely used in breast cancer patients to prevent tumor recurrence. Prior work has revealed a role of cytochrome and sulfotransferase enzymes in tamoxifen metabolism. In this descriptive study, correlations were examined between concentrations of tamoxifen metabolites and genotypes for CYP2D6, CYP3A4, CYP3A5, SULT1A1, SULT1A2 and SULT1E1 in 135 patients with estrogen receptor-positive breast cancer.

Tamoxifen therapy in breast cancer: do apolipoprotein E genotype and menopausal state affect plasma lipid changes induced by the drug?

Objective: This study examines the lipid profile change produced in response to tamoxifen (TAM) treatment, and its possible relationship with both apolipoprotein E genotype and menopausal state in patients with breast cancer.

Methods: Blood samples were collected from 86 Spanish women with breast cancer before initiating TAM treatment and in the following 6, 12 and 18 months of treatment. Plasma lipid levels (total cholesterol, triglycerides, HDL-cholesterol and LDL-cholesterol) were determined using an automatic analyzer.

Usefulness of autosomal STR polymorphisms beyond forensic purposes: data on Arabic- and Berber-speaking populations from central Morocco.

Background: This work describes, for the first time, the profile of Middle Atlas Berbers and Arabic-speaking central Moroccans for 15 autosomal STR loci widely used in forensic sciences.

Aim: The main objectives were to determine the degree of heterogeneity among different Moroccan samples to identify geographic or linguistic patterns and to evaluate the usefulness of forensic STRs in anthropological studies.

Subjects And Methods: Blood samples were collected from 71 Arabic-speakers and 75 Berbers from the regions of Doukkala (central-west coast) and Khenifra (Middle Atlas), respectively.

Polymorphisms influencing muscle phenotypes in North-African and Spanish populations.

Aim: The purpose of this study was to determine the allelic and genotypic frequency distribution of the C34T mutation in the muscle isoform of the adenosine monophosphate deaminase 1 (AMPD1) gene and of the missense substitution K153R in the myostatin (GDF8) gene in one Spanish and two North African populations.

Method: One sample of 98 individuals was genotyped from the South of Spain (Alpujarra) and two samples from Morocco (77 Berbers and 78 Arabs).

Results: The frequency of the AMPD1 C34T mutation was lower in Berbers (0.

CYP2D6*4 allele and breast cancer risk: is there any association?

Background: CYP2D6 is an important cytochrome P450 enzyme. These enzymes catalyse the oxidative biotransformation of about 25% of clinically important drugs as well as the metabolism of numerous environmental chemical carcinogens. The most frequent null allele of CYP2D6 in European populations, CYP2D6*4, has been studied here in order to elucidate whether a relationship exists between this allele and the risk of developing breast cancer in a Spanish population.

The clinical effectiveness and cost-effectiveness of genotyping for CYP2D6 for the management of women with breast cancer treated with tamoxifen: a systematic review.

Background: Breast cancer is the most common cancer affecting women in the UK. Tamoxifen (TAM) is considered as the standard of care for many women with oestrogen receptor positive breast cancer. However, wide variability in the response of individuals to drugs at the same doses may occur, which may be a result of interindividual genetic differences (pharmacogenetics).

Genetic differences among North African Berber and Arab-speaking populations revealed by Y-STR diversity.

Y-chromosome STR polymorphisms are inherited in a haploid state which makes them a powerful tool for easy tracing of paternal lineage and for use in human population evolutionary studies. North-African Y chromosomal diversity has traditionally been studied in order to find genetic and geographic associations as well as to test how natural and cultural barriers have affected the degree of genetic flow not only within North Africa but also in a wider Mediterranean context. The degree of Berber/Arab genetic differentiation in the Moroccan population has been tested for a complete set of forensic markers as sixteen Y-chromosomal short tandem repeats (STRs) (DYS19, DYS385, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635 and GATA H4.

CYP2D6 polymorphism screening in a selected population of Spain (La Alpujarra): no effect of geographical isolation.

Background: There is growing interest in the CYP2D6 gene because of its key role in the metabolism of numerous commonly used drugs.

Aim: We compared the frequency of the most frequent null CYP2D6 alleles (CYP2D6*3, CYP2D6*4,CYP2D6*5, CYP2D6*6, CYP2D6*7 and CYP2D6*8) between individuals from the Spanish population and from La Alpujarra.

Subjects And Methods: The present study comprises Spanish cohort (n = 185) and from La Alpujarra (n = 104).

STR genetic diversity in a Mediterranean population from the south of the Iberian Peninsula.

Sixteen Y-chromosomal short tandem repeats (STRs) (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635 and GATA H4.1) were typed in DNA samples from 52 unrelated men and 15 autosomal STRs (CSF1PO, D2S1338, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D19S433, D21S11, FGA, TH01, TPOX, vWA) were also studied for a group of 90 individuals (men and women) from the same population (Andalusians from La Alpujarra, South of Spain). The Alpujarrenian population represents an example of an isolated population with remarkable geographical, cultural and historical characteristics.