SERPINA1 Hepatocyte-Specific Promoter Polymorphism Associate with Chronic Obstructive Pulmonary Disease in a Study of Kashmiri Ancestry Individuals

Bashir, Aadil; Hazari, Younis; Bashir, Samirul; Hilal, Nazia; Banday, Mariam; Iqbal, Mir Khurshid; Jan, Tariq Rashid; Farooq, Syed Suraiya; Shah, Naveed Nazir; Fazili, Khalid Majid

doi:10.1007/s00408-018-0124-8

Cited by 3 publications

(2 citation statements)

References 12 publications

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“…In our previous study, the mean serum α1AT level in COPD cases carrying M3 variant on a promoter hepatocyte background (composite heterozygote) was found to be 1.20 ± 0.24 and 3.16 ± 0.16 g/L in cases and controls, respectively. The serum α1AT level in COPD cases was found to be 2.6 times less than the control group 13 . In this investigation, we explored this association further in context of M3-α1AT being largely considered as a normal variant of α1AT.…”

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confidence: 67%

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Aggregation of M3 (E376D) variant of alpha1- antitrypsin

Bashir

Hazari

Pal

et al. 2020

Sci Rep

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Alpha1-antitrypsin (α1AT) is an abundant serine-protease inhibitor in circulation. It has an important role in neutralizing the neutrophil elastase activity. Different pathogenic point mutations like Z(E342K)-α1AT have been implicated in the development of liver cirrhosis and Chronic Obstructive Pulmonary Disease (COPD), the latter being a cluster of progressive lung diseases including chronic bronchitis and emphysema. M3-α1AT (376Glu > Asp) is another variant of α1AT which so far is largely being considered as normal though increased frequency of the variant has been reported in many human diseases including COPD. We also observed increased frequency of M3-α1AT in COPD cases in Kashmiri population. The frequency of heterozygous (AC) genotype in cases and controls was 58.57% and 27.61% (odds-ratio 6.53 (2.27–15.21); p < 0.0001) respectively, while homozygous CC genotype was found to be 21.42% and 6.66% (odds-ratio 10.56 (3.63–18.64); p < 0.0001) respectively. Comparative in vitro investigations that include trypsin‒antitrypsin assay, Circular Dichroism spectroscopy and dynamic light scattering performed on wild-type (M-α1AT), M3-α1AT, and Z-α1AT proteins along with the molecular dynamics simulations revealed that M3-α1AT has properties similar to Z-α1AT capable of forming aggregates of varied size. Our maiden observations suggest that M3-α1AT may contribute to the pathogenesis of COPD and other disorders by mechanisms that warrant further investigations.

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confidence: 67%

“…Approximately, 2 mL of the venous blood sample was drawn from each participant in accordance to our established protocol 13 . The blood was collected in ethylene diamine-tetra-acetic acid-coated vials.…”

Section: Genomic Dna Extractionmentioning

confidence: 99%

Aggregation of M3 (E376D) variant of alpha1- antitrypsin

Bashir

Hazari

Pal

et al. 2020

Sci Rep

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Regional experience of a comprehensive dynamic assessment of the adolescents’ health status with post-COVID-19 syndrome during aftercare in a sanatorium

Mokina¹,

Mokin²

2023

Vopr. kurortol. fizioter. lech. fiz. kul't.

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Comparative Risk-Oriented Integrated Assessment of Lung Health Status in Preventive Planning of Rehabilitation Treatment Programs in a Sanatorium

Mokin

Mokina

2022

Vestnik "Biomedicina i sociologiya"

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Introduction. COPD is a heterogeneous disease, the variability and diversity of which depends on a combination of genetics and risk factors. At present, during the period of the deciphered human genome, an earlier assessment of the prognostic risk of the development of cochlea in young people is needed to understand the possibilities of establishing reversible lung lesions. Aim as a part of preventive phenotyping in young people; substantiate the importance of a comparative risk-oriented complex epigenetic and genetic assessment of the lung health status for predictive assessment of the risk of developing COPD. Materials and methods. In this cohort study, 293 young people (11-23 years old) took part, including 142 male and 151 female, who were divided into four groups. 1st group - 132 conditionally healthy non-smokers (51 male and 81 female), 2nd - 54 conditionally healthy smokers (39 male and 15 female), 3rd - 86 non-smokers, with chronic lung diseases (52 persons – chronical tracheobronchitis; 43 persons – bronchial asthma), 4th - 21 smokers with chronic lung diseases (HRTB - 12 persons, BA - 9 persons). To assess the differences in epigenetic and genetic criteria, methods such as spirometry, gas analysis, electronic auscultation, digital acoustic analysis of respiratory work, analysis of gene polymorphisms for the alpha1-antitrypsin-SERPINA-1 complex in venous blood serum were used. We have developed a computer program, taking into account the risk factors for the prognostic development of COPD in a cohort of smoking and non-smoking young people aged 11-23 years with or without a diagnosis of chronic lung disease. Results. Among the most reliable, informative, sensitive and specific phenotyping indicators in assessing the prognostic degree of COPD risk in adolescents: cough, sputum production, ARI frequency per year, smoking index, electronic auscultation data, FEV1%, FVC%, FEV1 / FVC%, CO, O2, AAT, SERPINA. These criteria made up the characteristics of risk phenotypes, which allows the subjects to be graded according to groups (phenotypes) of the prognostic risk of COPD - low, moderate, high or extremely high, depending on the scale of criterion values. In young people in the context of predictive preventive personalized medicine. This made it possible to draw up an algorithm for assessing risk groups and a computer program based on this algorithm, which makes it possible to determine the phenotypes of COPD risk in young people. Conclusion: Starting from adolescence, it is possible to record the initial functional disorders of the respiratory status in combination with genetic polymorphisms, which confirms the need for preventive screening for the primary identification of risk groups and the formation of preventive programs in young people. The developed algorithm and computer program make it possible to determine the prognostic risk of COPD in young people - from low to moderate, high and extremely high, in terms of the implementation of the concept of 3P (personalized, preventive, and predictive) medicine.

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SERPINA1 Hepatocyte-Specific Promoter Polymorphism Associate with Chronic Obstructive Pulmonary Disease in a Study of Kashmiri Ancestry Individuals

Cited by 3 publications

References 12 publications

Aggregation of M3 (E376D) variant of alpha1- antitrypsin

Aggregation of M3 (E376D) variant of alpha1- antitrypsin

Regional experience of a comprehensive dynamic assessment of the adolescents’ health status with post-COVID-19 syndrome during aftercare in a sanatorium

Comparative Risk-Oriented Integrated Assessment of Lung Health Status in Preventive Planning of Rehabilitation Treatment Programs in a Sanatorium

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