Plenaxis (abarelix) / Contura - LARVOL DELTA

GnRH Peptide Antagonist: Comparative Analysis of Chemistry and Formulation with Implications for Clinical Safety and Efficacy. (PubMed, Pharmaceuticals (Basel)) - "Key GnRH peptide antagonists authorized by the regulatory agencies include Cetrorelix, Ganirelix, Abarelix, Degarelix, and Teverelix. All GnRH peptide-based antagonists were analyzed in detail for formulation strategy, pharmacokinetics, effectiveness, and safety. This review also emphasizes GnRH antagonists' clinical promise, providing insights into their evolution and the possibility for future research in developing safer, more effective treatments for complicated hormonal diseases."

Journal • Review • Cardiovascular • Endometriosis • Genito-urinary Cancer • Gynecology • Oncology • Prostate Cancer • Solid Tumor • Uterine Leiomyoma • Women's Health

Efflux pump gene single nucleotide variants associated with resistance in Mycobacterium tuberculosis isolates with discrepant drug genotypes. (PubMed, J Glob Antimicrob Resist) - "Considering SNVs in efflux pumps as part of MTB genome-based resistance interpretation may add value especially in evaluation of XDR resistance in strains with phenotype-genotype discrepancies."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Urology Times Innovation Celebration: Expert Insights - Episode 27: Dr. Crawford on LHRH analogues in prostate cancer (Urology Times) - "n this interview, E. David Crawford, MD, discusses the development of luteinizing hormone-releasing hormone agonists and antagonists in prostate cancer."

Interview

Current and emerging gonadotropin-releasing hormone (GnRH) antagonists for the treatment of prostate cancer. (PubMed, Expert Opin Pharmacother) - "Emerging data regarding benefit of the use of GnRH antagonists in patients with concomitant cardiovascular disease are of great interest. Relugolix has emerged as the first orally administered GnRH antagonist able to achieve and maintain testosterone castration levels and it is associated with a profound reduction of major cardiovascular events."

Journal • Cardiovascular • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

[VIRTUAL] Proteomics Identified Novel Proteins Associated With Genetic Risk Of Abdominal Aortic Aneurysm: The Atherosclerosis Risk In Communities Study (ARIC) (EPI-LIFESTYLE 2021) - "A recent genome-wide association study identified and replicated nine AAA-related variants (rs602633, rs4129267, rs3827066, rs1795061, rs10757274, rs10985349, rs9316871, rs6511720, and rs2836411), but pathways through which these loci may influence disease have not been elucidated... Three of the nine AAA risk variants were associated with plasma protein concentrations, with the strongest associations for those involved in inflammation, endothelial dysfunction, and extracellular matrix remodeling. Granulin, complement C1q tumor necrosis factor-related protein-1, kit ligand, and neogenin represent novel targets for genetic risk of AAA and may link genetic susceptibility to disease pathogenesis."

Atherosclerosis • Cardiovascular • Dyslipidemia • Immunology • Inflammation • Oncology • C1Q • IL6R • MMP9

Whole-Exome Sequencing Identifies Small Mutations in Pakistani Muscular Dystrophy Patients. (PubMed, Genet Test Mol Biomarkers) - "One missense variant c.3406A>T (rs3827462) and a nonsense variant c.4375C>T (rs398123953) were not detected in our cohort of 18 dystrophinopathy patients. Whole-exome sequencing identified a nonsense variant in Pakistani muscular dystrophy patients, which is amenable to treatment by Ataluren and a missense variant in YARS2 gene responsible for causing MLASA."

Clinical • Journal • Duchenne Muscular Dystrophy • Genetic Disorders • Hematological Disorders • Metabolic Disorders • Muscular Dystrophy • Myositis

The human EDAR 370V/A polymorphism affects tooth root morphology potentially through the modification of a reaction-diffusion system. (PubMed, Sci Rep) - "Recent studies have clarified that a nonsynonymous variant in the ectodysplasin A receptor gene (EDAR 370V/A; rs3827760) contributes to crown traits related to Sinodonty...The computational study suggested that the complicated effects of the EDAR polymorphism could be explained when it is considered that EDAR modifies the syntheses of multiple related molecules working in the reaction-diffusion dynamics. In this study, we shed light on the molecular mechanisms of tooth root morphogenesis, which are less understood in comparison to those of tooth crown morphogenesis."

Journal • Immunology

Genetic polymorphisms in collagen-related genes are associated with pelvic organ prolapse. (PubMed, Menopause) - "We are the first to evaluate the relationship between COL14A1, COL5A1, and COL4A2 polymorphisms and POP, besides COL3A1, COL1A1, and COL18A1, which have been reported previously. We found several candidate SNPs that were significantly associated with prolapse in Chinese women. Our results provide new evidence for further investigation of the involvement of these potential genes in the etiology of POP."

Journal

The interaction between MALAT1 target, miR-143-3p, and RALGAPA2 is affected by functional SNP rs3827693 in breast cancer. (PubMed, Hum Cell) - "The rs3827693 allele G significantly decreased the breast cancer incidence and augmented the negative correlation between RALGAPA2 and miR-143-3p, presumably through strengthening the interaction between these two transcripts. This study proposed MALAT1 miR-143-3p and miR-143-3p RALGAPA2 axis in breast cancer, whereby the latter can be altered by the clinically functional SNP rs3827693."

Journal • Breast Cancer • Oncology • Solid Tumor

Erythropoietin-producing hepatocellular A7 restrains estrogen-negative feedback of luteinizing hormone via ephrin A5 in the hypothalamus of female rats. (PubMed, Am J Physiol Endocrinol Metab) - "Various rat models (OVX, E-treated OVX, and abarelix treated) were injected with the recombinant EPHA7-Fc protein through the caudal vein to investigate the molecular mechanism underlying the promotion of LH secretion by EPHA7...In addition, the systemic administration of EPHA7-Fc restrained the inhibition of Efna5 and Gnrh1 by E, resulting in increased Efna5 and Gnrh1 expression in the hypothalamus, as well as increased serum LH levels. Collectively, our findings demonstrated the involvement of EPHA7-EFNA5 signaling in the regulation of LH and the E-negative feedback pathway in the hypothalamus, highlighting the functional role of EPHA7 in female reproduction."

Journal • Preclinical

Is it possible ABC transporters genetic variants influence the outcomes of a weight-loss diet in obese women? (PubMed, Genet Mol Biol) - "It was investigated whether SNPs in the ABCA1 (rs1800977 and rs2230806), ABCA7 (rs2279796) and ABCG1 (rs692383 and rs3827225) genes can modulate the responsiveness of 137 obese women to a weight-loss dietary intervention...Regarding the longitudinal analysis, after multi-test correction, the association remained between ABCG1 rs692383 G allele and HDL-c levels: G allele carriers had a lower HDL-c reduction (p = 0.043). Results suggest the standard weight-loss diet applied in this study could attenuate the ABCA7 rs2279796 GG genotype effects found at baseline and non-dyslipidemic obese women with ABCG1 rs692383 G allele are benefitting from the diet with a lower reduction in HDL-c levels."

Clinical • Journal • Genetic Disorders • Obesity

GPR174 and ITM2A Gene Polymorphisms rs3827440 and rs5912838 on the X chromosome in Korean Children with Autoimmune Thyroid Disease. (PubMed, Genes (Basel)) - "In male AITD patients, rs3827440 T and rs5912838 A were susceptible and rs3827440 C and rs5912838 C were protective genotypes. (4) Polymorphisms in GPR174 and ITM2A genes on the X chromosome might be associated with AITD in Korean children."

Clinical • Journal • Endocrine Disorders • Immunology • Ophthalmology

Genetic variants in glutamate cysteine ligase confer protection against type 2 diabetes. (PubMed, Mol Biol Rep) - "This study investigated whether single nucleotide polymorphisms (SNPs) at genes encoding glutamate cysteine ligase catalytic (rs12524494, rs17883901, rs606548, rs636933, rs648595, rs761142 at GCLC) and modifier (rs2301022, rs3827715, rs7517826, rs41303970 at GCLM) subunits are associated with susceptibility to type 2 diabetes...Three SNPs rs17883901, rs636933, rs648595 at GCLC and one rs2301022 at GCLM were associated with decreased levels of ROS, while SNPs rs7517826, rs41303970 at GCLM were associated with increased levels of total GSH in plasma. Single nucleotide polymorphisms in genes encoding glutamate cysteine ligase subunits confer protection against type 2 diabetes and their effects are mediated through increased levels of glutathione."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Effects of HTR1B 3' region polymorphisms and functional regions on gene expression regulation. (PubMed, BMC Genet) - "The 3' region of HTR1B has a regulatory effect on gene expression, which is likely closely associated with the interpretation of HTR1B-related disorders. In addition, the HTR1B 3' region includes several effector binding sites that induce an inhibitory effect on gene expression."

Journal • CNS Disorders • Psychiatry

[VIRTUAL] Associations of GPR174 and ITM2A Genes on X Chromosome with Early Onset Autoimmune Thyroid Disease in Korean (ENDO-I 2020) - "In AITD, the frequencies of GPR174 rs3810711 T allele (OR=6.0, cP =0.000), GRP174 rs3827440 T allele (OR=6.0, cP =0.000), ITM2A-GPR174 rs5912838 A allele (OR=2.7, cP =0.001) were increased and of GPR174 rs3810711 CC genotype (OR=0.2, cP =0.000), GRP174 rs3827440 CC genotype (OR=0.2, cP =0.000), ITM2A-GPR174 rs5912838 CC genotype (OR=0.4, cP =0.000)were lower than controls. In GD, the frequencies of GPR174 rs3810711 T allele (OR=8.4, cP =0.000), GRP174 rs3827440 T allele (OR=8.4, cP =0.000), ITM2A-GPR174 rs5912838 A allele (OR=3.3, cP =0.000) were increased and GPR174 rs3810711 CC genotype (OR=0.1, cP =0.000), C allele (OR=0.5, cP =0.044), GRP174 rs3827440 CC genotype (OR=0.2, cP =0.000), C allele (OR=0.5, cP =0.044), ITM2A-GPR174 rs5912838 CC genotype (OR=0.4, cP =0.000) were lower than controls. In HD, the frequencies of GPR174 rs3810711 T allele (OR=3.9, cP =0.003), GRP174 rs3827440 T allele(OR=3.9, cP =0.003) were increased and GPR174 rs3810711 CC genotype (OR=0.3, cP..."

Endocrine Disorders • Immunology • Ophthalmology

Characterisation of a second gain of function EDAR variant, encoding EDAR380R, in East Asia. (PubMed, Eur J Hum Genet) - "From functional studies in cultured cells, we find that EDAR:p.(Ser380Arg) displays increased EDAR signalling output, at a similar level to that of EDAR:p.(Val370Ala). The existence of a second SNV with partly overlapping geographic distribution, the same in vitro functional effect and similar evolutionary age as the derived allele of rs3827760, but of independent origin and not exhibiting the same signs of strong selection, suggests a northern focus of positive selection on EDAR function in East Asia."

Journal

New treatment paradigm for prostate cancer: Abarelix initiation therapy for immediate testosterone suppression followed by a luteinizing hormone-releasing hormone agonist (BJU Int) - P=NA, N=176; At the end of the abarelix treatment period (day 85), 93.8% of pts achieved castrate levels, during the first week of switch over to the LHRH agonist therapy (days 85-92) the rate was 86.5% a& during the week after the second LHRH agonist injection (days 114-12) it was 93.3%; Mean PSA levels decreased from 20.5 (56.6) ng/mL at baseline to 3.7 (23.5) ng/mL on day 85 & remained stable throughout the LHRH agonist treatment phase

Clinical data • Oncology

Integrative approach identifies corticosteroid response variant in diverse populations with asthma. (PubMed, J Allergy Clin Immunol) - "African Americans and Latinos are disproportionately affected by asthma and its complications. Here we identify a pharmacogenomic variant that may assist in identifying individuals from these groups who will respond to ICS treatment."

Clinical • Journal

Replication of Newly Identified Genetic Associations Between Abdominal Aortic Aneurysm and SMYD2, LINC00540, PCIF1/MMP9/ZNF335, and ERG. (PubMed, Eur J Vasc Endovasc Surg) - "Associations between rs9316871and rs2836411 and AAA risk were replicated in the meta-analysis of the two independent cohorts, providing further support for the importance of these loci in the aetiology of AAA."

Journal

Associations of GPR174 and ITM2A Genes on X Chromosome with Early Onset Autoimmune Thyroid Disease in Korean. (ENDO 2020) - "In AITD, the frequencies of GPR174 rs3810711 T allele (OR=6.0, c P =0.000), GRP174 rs3827440 T allele (OR=6.0, c P =0.000), ITM2A-GPR174 rs5912838 A allele (OR=2.7, c P =0.001) were increased and of GPR174 rs3810711 CC genotype (OR=0.2, c P =0.000), GRP174 rs3827440 CC genotype (OR=0.2, c P =0.000), ITM2A-GPR174 rs5912838 CC genotype (OR=0.4, c P =0.000)were lower than controls. In GD, the frequencies of GPR174 rs3810711 T allele (OR=8.4, c P =0.000), GRP174 rs3827440 T allele (OR=8.4, c P =0.000), ITM2A-GPR174 rs5912838 A allele (OR=3.3, c P =0.000) were increased and GPR174 rs3810711 CC genotype (OR=0.1, c P =0.000), C allele (OR=0.5, c P =0.044), GRP174 rs3827440 CC genotype (OR=0.2, c P =0.000), C allele (OR=0.5, c P =0.044), ITM2A-GPR174 rs5912838 CC genotype (OR=0.4, c P =0.000) were lower than controls. In HD, the frequencies of GPR174 rs3810711 T allele (OR=3.9, c P =0.003), GRP174 rs3827440 T allele(OR=3.9, c P =0.003) were increased and GPR174 rs3810711 CC..."

Melanocortin 3 receptor gene polymorphism is associated with polycystic ovary syndrome in Turkish population. (PubMed, Gynecol Endocrinol) - "Anthropometric measurements, physical examination results, laboratory findings, and hormone levels were recorded for each participant and analysis of two SNPs on the MC3R gene; rs3746619 and rs3827103 were performed...Two polymorphisms did not found related to obesity and insulin resistance in PCOS subgroups analysis. MC3R gene rs 3746619 polymorphism was found associated with PCOS in the Turkish population and may make a contribution to the genetic baseline of the disease."

Clinical • Journal

Genome-wide association study in Japanese females identifies fifteen novel skin-related trait associations. (PubMed, Sci Rep) - "A known hair morphology signal in EDAR was associated with both eyebrow thickness (rs3827760; P = 1.7 × 10) and straight/curly hair (rs260643; P = 1.6 × 10)...In total, we identified twelve loci containing sixteen association signals, of which fifteen were novel. These findings will help dermatologic researchers better understand the genetic underpinnings of skin-related phenotypic variation in human populations."

IO Biomarker • Journal

EDAR, LYPLAL1, PRDM16, PAX3, DKK1, TNFSF12, CACNA2D3, and SUPT3H gene variants influence facial morphology in a Eurasian population. (PubMed, Hum Genet) - "...These included EDAR rs3827760, LYPLAL1 rs5781117, PRDM16 rs4648379, PAX3 rs7559271, DKK1 rs1194708, TNFSF12 rs80067372, CACNA2D3 rs56063440, and SUPT3H rs227833...The majority of these SNPs showed a distinct allele frequency between European and East Asian reference panels from the 1000 Genomes Project. These results showed the details of above eight genes influence facial shape variation in a Eurasian population."

Clinical • Journal

Mitogen-activated protein kinase eight polymorphisms are associated with immune responsiveness to HBV vaccinations in infants of HBsAg(+)/HBeAg(-) mothers. (PubMed, BMC Infect Dis) - "MAPK8 polymorphisms are associated with immune response to HBV vaccinations in infants of HBsAg(+)/HBeAg(-) mothers."

Journal

Identification of SEPTIN12 as a novel target of the androgen and estrogen receptors in human testicular cells. (PubMed, Biochimie) - "...Two single nucleotide polymorphisms (SNPs), rs759992 T > C and rs3827527 C > T, were observed in the SEPT12 gene promoter region and were able to decrease the promoter activity. In conclusion, the current work identified the promoter of the human SEPT12 gene and provided key evidence about its transcriptional regulation via E2 and 5α-DHT. Since SEPT12 has an important role in spermatogenesis, SEPT12 expression analysis can be developed as a potential tool for the assessment of environmental or food pollution by hormones or for the evaluation of the risk of endocrine-disrupting chemicals (EDCs) in general."

Journal