LZTFL1: Babban Haɗari COVID-19 Gene gama gari zuwa Asiya ta Kudu An Gano

Bayyanar LZTFL1 yana haifar da yawan TMPRSS2, ta hanyar hana EMT (canjin epithelial mesenchymal), wani martani na ci gaba da ke da hannu wajen warkar da rauni da kuma murmurewa daga cuta . Kamar yadda yake a TMPRSS2, LZTFL1 yana wakiltar wani magani da za a iya amfani da shi don ƙirƙirar sabbin magunguna don yaƙi da COVID-19.

Cutar COVID-19 ta haifar da mummunar barna ga miliyoyin mutane a duniya, wanda ya haifar da mutuwar miliyoyin mutane a duk duniya, kuma ya kawo cikas ga tattalin arzikin yawancin ƙasashe. Nazarin bincike a cikin shekaru 2 da suka gabata ya haifar da ci gaba mai mahimmanci a fahimtar cutar, wanda ya haifar da gano magungunan da ake amfani da su don samar da maganin COVID-19 da kuma haɓaka ingantattun alluran rigakafi don hana yaɗuwar cutar. Duk da haka, har yanzu ba mu da isasshen lokaci don fahimtar cutar da SARS-CoV-2 ke haifarwa, kuma ƙarin bincike yana da mahimmanci kuma ana ci gaba da yin sa don samun fahimtar iliminmu game da COVID-19.

A cikin wani takarda da aka buga jiya a cikin Nature Genetics, masu bincike sun gano kwayar halittar LZTFL1 (leucine zipper transcription factor kamar 1) wacce za a iya dangantawa da haifar da mummunan cutar COVID-19 ga mutanen asalin Kudancin Asiya. Wannan ya yiwu ne ta hanyar yin nazarin GWAS (nazarin haɗin gwiwar kwayoyin halitta) ta amfani da gwaje-gwajen lissafi da na dakin gwaje-gwaje da kuma gano wani yanki na chromosome na ɗan adam 3p21.31 a matsayin wanda ke da mafi ƙarfi da kuma haifar da saurin kamuwa da cuta tare da COVID-19 ^1. Bambancin kwayoyin halitta a cikin kwayoyin halittar da ke cikin yankin 3p21.31 yana gabatar da haɗarin gazawar numfashi sau biyu daga COVID-19 ^2. Bugu da ƙari, bambancin kwayoyin halitta a cikin wannan wurin chromosome yana ɗauke da fiye da kashi 60% na mutane tare da asalin Kudancin Asiya (SAS), idan aka kwatanta da 15% na ƙungiyoyin zuri'a (EUR). Wannan na iya zama ɗaya daga cikin dalilan da ke bayyana ci gaba da yawan kamuwa da cuta da kuma yawan mace-mace a cikin wannan al'umma a ƙasashe kamar UK ^3,4.

LZTFL1 ɗaya ne daga cikin irin wannan kwayar halitta da ke da alaƙa da wurin 3p21.31 kuma yawan bayyanarsa da ba a saba gani ba wanda ya haifar da hulɗar mai haɓaka rs1773054 tare da mai haɓaka LZTFL1 yana da mummunan tasiri ga cutar COVID-19 wanda ke sa mutane su zama masu saurin kamuwa da cuta mai tsanani. Ƙara yawan bayyanar LZTF1 yana hana EMT (canjin epithelial mesenchymal) ⁵ , hanyar ci gaba wadda ke kunna ta hanyar amsawar ƙwayoyin cuta kuma tana taka muhimmiyar rawa a cikin amsawar rigakafi ta asali da kuma murmurewa daga kamuwa da cuta. Rage bayyanar LZTFL1 yana haɓaka EMT ⁶ wanda ke haifar da yaduwar ƙwayoyin epithelial don gyara kyallen da suka lalace, ta haka ne ke shawo kan cutar. A cikin mahallin kamuwa da cutar SARS-CoV-2, EMT kuma yana haifar da raguwar ƙimar mai karɓar ACE2 da TMPRSS2 (nau'in 2 serine membrane protease) wanda ke hana shigar ƙwayoyin cuta cikin ƙwayoyin epithelial na huhu. Akasin haka, hana EMT da ƙaruwar matakan LZTFL1 ke haifarwa yana haifar da ƙaruwar matakan ACE2 da TMPRSS2, ta haka yana haɓaka shigar ƙwayoyin cuta da haifar da mummunan cutar COVID-19. Ana buƙatar ƙarin bincike don samun ƙarin fahimta game da rawar da hanyar EMT ke takawa da LZTFL1 a cikin mahallin haifar da cututtukan huhu.

Kwanan nan, mun tattauna mahimmancin TMPRSS2 a matsayin wani abu da zai iya zama sanadin magani da kuma ci gaban MM3122, wani sabon magani da ake amfani da shi wajen magance COVID-19 ^7. Babban bayyanar LZTFL1 shi ma yana haifar da babban matakin TMPRSS2, ta hanyar hana EMT ^8. Kamar yadda yake a TMPRSS2, LZTFL1 kuma yana wakiltar wani abu da za a iya amfani da shi wajen samar da sabbin magunguna a kan COVID-19.

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References: 

1. Downes, DJ, Cross, AR, Hua, P. et al. Gano LZTFL1 azaman ɗan takara mai tasiri gene a wurin haɗarin COVID-19. Nat Genet (2021). https://doi.org/10.1038/s41588-021-00955-3 

2. Ellinghaus, D. et al. Nazarin ƙungiyar Genomewide na mai tsanani COVID-19 tare da gazawar numfashi. N. Engl. J. Med. 383, 1522-1534 (2020). DOI: https://doi.org/10.1056/NEJMoa2020283 

3. Nafilyan, V., Islam, N., Mathur, R. et al. Bambance-bambancen kabilanci a cikin mace-macen COVID-19 a lokacin raƙuman ruwa biyu na farko na Cutar Kwayar cuta ta Coronavirus: nazarin ƙungiyar gamayya na ƙasa baki ɗaya na manya miliyan 29 a Ingila. Eur J Epidemiol 36, 605-617 (2021). https://doi.org/10.1007/s10654-021-00765-1 

4. Richards-Belle, A., Orzechowska, I., Gould, DW et al. Gyara zuwa: COVID-19 a cikin kulawa mai mahimmanci: cututtukan cututtukan cututtukan cututtukan farko a fadin Ingila, Wales da Ireland ta Arewa. Kulawa Mai Tsanani Med 47, 731-732 (2021). https://doi.org/10.1007/s00134-021-06413-2  

5. Kalluri, R. & Weinberg, RA Tushen canjin epithelial-mesenchymal. J. Clin. Sanya jari. 119, 1420-1428 (2009). DOI: https://doi.org/10.1172/JCI39104  

6. Wei, Q., Chen, ZH., Wang, L. et al. LZTFL1 yana hana ƙwayar cutar huhu ta hanyar kiyaye bambance-bambancen ƙwayoyin epithelial na huhu. Oncogene 35, 2655-2663 (2016). https://doi.org/10.1038/onc.2015.328 

7. Soni R. 2012. MM3122: Jagoran Dan takara don Novel Antiviral magani don COVID-19. Kimiyyar Turai. An buga akan 1 Nuwamba 2021. Akwai akan layi a http://scientificeuropean.co.uk/sciences/biology/mm3122-a-lead-candidate-for-novel-antiviral-drug-against-covid-19/ 

8. Wani, Q. et al. Tumor-suppressive ayyuka na leucine zik din rubutu factor-kamar 1. Cancer Res. 70, 2942-2950 (2010). DOI: https://doi.org/10.1158/0008-5472.CAN-09-3826 

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