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1.
Mol Biol Rep ; 50(5): 4309-4316, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36920597

RESUMEN

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has emerged as a serious public health emergency of global concern. Angiotensin converting enzyme 2 (ACE2) peptidase domain is important for the cellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Germline variants in ACE2 peptidase domain may influence the susceptibility for SARS-CoV-2 infection and disease severity in the host population. ACE2 genetic analysis among Caucasians showed inconclusive results. This is the first Asian study investigating the contribution of ACE2 germline variants to SARS-CoV-2 infection in Pakistani population. METHODS: In total, 442 individuals, including SARS-CoV-2-positive (n = 225) and SARS-CoV-2-negative (n = 217) were screened for germline variants in ACE2 peptidase domain (exons 2, 3, 9, and 10) using high resolution melting and denaturing high-performance liquid chromatography analyses followed by DNA sequencing of variant fragments. The identified variant was analyzed by in silico tools for potential effect on ACE2 protein. RESULTS: A missense variant, p.Lys26Arg, was identified in one SARS-CoV-2-positive (1/225; 0.4%) and three SARS-CoV-2-negative (3/217; 1.4%) individuals. No significant difference in the minor allele frequency of this variant was found among SARS-CoV-2-positive and SARS-CoV-2-negative individuals (1/313; 0.3% versus 3/328; 0.9%; P = 0.624), respectively. The SARS-CoV-2-positive patient carrying p.Lys26Arg showed mild COVID-19 disease symptoms. It was predicted as benign variant by in silico tool. No variant was detected in ACE2 residues important for binding of SARS-CoV-2 spike protein. CONCLUSION: The p.Lys26Arg variant may have no association with SARS-CoV-2 susceptibility in Pakistani population. Whole ACE2 gene screening is warranted to clarify its role in SARS-CoV-2 infection.


Asunto(s)
Enzima Convertidora de Angiotensina 2 , COVID-19 , Humanos , Enzima Convertidora de Angiotensina 2/genética , COVID-19/genética , Pakistán/epidemiología , Unión Proteica , SARS-CoV-2/genética
2.
HPB (Oxford) ; 24(12): 2134-2144, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36175305

RESUMEN

BACKGROUND: Partner and localizer of BRCA2 (PALB2) is a pancreatic cancer (PC) susceptibility gene reported in Caucasians. However, limited data are available among Asians. We investigated the contribution of PALB2 germline variants to Pakistani PC patients. METHODS: 150 unselected and prospectively enrolled PC patients were comprehensively screened for PALB2 variants, using denaturing high-performance liquid chromatography and DNA sequencing. Novel variants were investigated for their pathogenic effect using in-silico tools. Potentially functional variants were screened in 200 controls. RESULTS: Twenty-two different PALB2 variants were identified. A missense variant (p.Arg37His) was identified in a 48-years-old male patient with a family history of breast cancer. Another missense variant (p.Trp898Arg) was identified in a 48-years-old male patient with a family history of esophageal cancer. A novel 3' downstream variant (c.∗480A>G) was detected in a 34-years-old female patient with family history of lung cancer. Another novel 3' downstream variant (c.∗417A>C) was identified in a 41-years-old male patient. All these variants were absent in 200 controls. p.Arg37His and p.Trp898Arg were predicted as likely pathogenic. c.∗417A>C and c.∗480A>G were classified as variants of uncertain significance. CONCLUSION: This is the first study that suggests a minimal contribution of PALB2 variants to PC risk in Pakistani population.


Asunto(s)
Proteína del Grupo de Complementación N de la Anemia de Fanconi , Neoplasias Pancreáticas , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Mutacional de ADN , Proteína del Grupo de Complementación N de la Anemia de Fanconi/genética , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas
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