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Journal : Narra J

CTLA-4 +6230G>A polymorphism and its impact on CTLA-4 level and risk of hepatocellular carcinoma: A case-control study in Batak patients with chronic hepatitis B Darmadi, Darmadi; Rey, Imelda; Lubis, Masrul; Lindarto, Dharma; Muzasti, Riri A.
Narra J Vol. 5 No. 2 (2025): August 2025
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v5i2.1959

Abstract

Genetic polymorphisms in cytotoxic T-lymphocyte-associated protein 4 gene (CTLA-4) vary by ethnic background, necessitating population-specific studies. The aim of this study was to assess the association between the CTLA-4 +6230G>A polymorphism, serum CTLA-4 level, and hepatocellular carcinoma (HCC) in Batak patients with chronic hepatitis B, a group with high hepatitis B virus (HBV) endemicity. A case-control study was conducted among cases (Batak patients with chronic hepatitis B and HCC) and controls (chronic hepatitis B without HCC). Genotyping of the CTLA-4 +6230G>A polymorphism was performed using the TaqMan SNP Genotyping Assay. Serum CTLA-4 level was quantified using enzyme-linked immunosorbent assay (ELISA). Patient’s demographic, clinical and laboratory data were recorded and assessed including age, sex, body mass index (BMI), smoking history, cirrhosis status, HBV DNA level, liver function markers (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)), hepatitis B e-antigen (HBeAg) status, smoking history, and alcohol consumption. This study found that G allele was significantly associated with an increased risk of HCC (OR: 2.69; 95%CI: 1.21–6.00; p=0.013). Individuals with GG/AG genotypes had a 2.89-fold higher risk of developing HCC compared to those with the AA genotype (p=0.032). Serum CTLA-4 level was significantly elevated in G allele carriers (GG: 159.9±57.1 pg/mL vs AA: 83.7±44.7 pg/mL; p<0.001). Multivariate analysis identified cirrhosis as the strongest predictor of HCC (OR: 7.60; p<0.001), followed by elevated ALT (OR: 3.42; p=0.018) and high HBV DNA levels (OR: 2.31; p=0.024). In conclusion, the CTLA-4 +6230G>A GG/AG genotype and elevated serum CTLA-4 level were significantly associated with an increased risk of HCC in Batak individuals with chronic HBV infection. Further research is needed to explore additional CTLA-4 polymorphisms and immune regulatory mechanisms in HBV-related HCC to improve risk stratification and therapeutic strategies.
Co-Authors Abdul Aziz Adi Wibowo Adisalamun Adisalamun Agus Suhartono Agustin, Adinda Eka Ahyani, Ahyani Alhuda Amelia, Resty Ayu Andriani, Laura Ikhsa Anwar Thaib Ariska, Maiata Devi Arnentis Arnentis, Arnentis Aryuningtias, Inda Rizky Asiska Permata Dewi Asmara, Josi Farda Khafid Astuti, Indra Puji Audia, Clara Ayu, Giovanni Ayuningtias, Ratih Baehaqi Balqist, Tanaya Barus, Rona Ganta Benny Handoyo, Benny Brilian Dini Ma. Iballa Budiono Budiono Budiyono Budiyono Choirunnisa, Nastiti Cut Meurah Rosnelly Dahnilsyah, Dahnilsyah Daliani, Putri Darmawati Darmawati Destiana, Ristian Diva Dewi Permata Sari dharma Lindarto, dharma Dhoti, Shofi Ma'rifaturriya Diana Natalia Dianti, Putri Rahma Dipuja, Diah Anugrah Divi Handoko Diyah, Anggraeni Djati, Sri Sasmita Djati, Sri Sasmito Donalizarti, Donalizarti Dorti Faot Dwi Rohman Soleh, Dwi Rohman Edi Sudrajat Eliyani, Fitri Endang Purwaningsih Endarwati, Tri Erida, Zulfa Ermina Sari Ernidawati, Ernidawati Evi Suryawati Fadhilla, Febriana Nor Fadila, Sarah Faisal Haitomi Faizin, T. Faizin Fani, Syahmila Nanda Farhani, Lailatul Farid Farid, Farid Fathan, Muhammad Fashanul Fatihah, Salsabilla Rima Fatimah, Dafina Febiana, Maissy Feriandi, Yoga Ardian Fitra Suzanti Fitri, Ailsa Fitriana, Elza Fitriana, Nimas Nur Fitriyadi, Enjah Pipit Fitriyani, Novi Yanti Duwi Gaho, Daratul Aini Giovanni, Giovanni Gontar Alamsyah Siregar Gunarda, Gunarda Guruh, Muhamad Hafit, Muhammad Fairuz Asra Halomoan, Yan Kristian Hariyanti, Mariya Keke Hasan, Dedy Haryadi Hasbullah Hasbullah Herlina, Sara Hery Widijanto Hesti Meilina Husni Husin I Gusti Bagus Wiksuana Idris Idris Imelda Rey Imma Widyawati Agustin Indah, Erika Irda Sayuti IRWANTO Isa, M ismaningsih, ismaningsih Jelita, Aulia Vinda Junaedi Abdillah, Junaedi Junizar, Herdya Juwita, Sellia Kamaludin, Insan Kamaruzzaman, Suraiya Kustini, Endang Kusuma, Debby Widya Kusuma, Rinda Tri lakantina, Sherly Lenny Prastiyowati, Lenny Leonardo Basa Dairi Lestari, Aulia Liantoro, Liantoro M, Iqhramullah M, Irfan M. Yogi Riyantama Isjoni Mahidin Mahidin Mariani Natalina Mariani Natalina L, Mariani Masrul Lubis Mawaddah , Nurul Medyan Riza Mirna Rahmah Lubis Mitri Irianti Moch. Rifai Muhammad Hatta Muhammad Rifai Muhammad Saleh Muhammad Zainul Arifin Muhammad Zaki Mujahidah, Lathifah Mujiastutik, Dhea Putri Murtafi’ah, Wasilatul Muslim*, Abrar Musriyani, Iin Muzasti, Riri A. Nabil Nabil, Nabil Nadia Rahmadhani Naila Fauza Napitupulu, Romauli Juliana Nartini, Nartini Natalia, Dilla Natalina. L, Mariani Nur Aysah, Ervinda Ika Nur, Doni Haidar Nurhazanah, Nurhazanah Nursal Nursal, Nursal Pamungkas, Dimas Tri Patmawati, Ike Permata Dewi, Asiska Pertiwi, Hernin Diah Permata Pocut Nurul Alam Prasetyo, Yohannes Eko Pratama, Aidilla Putri Nanda Pratama, Guruh Dwi Pratikso Pratikso Priyandani, Marisa Ayu Priyatna, Priyatna Pujiastutik, Novi Purba, Ernova Viorely Purbayani, Dina Rizky Purwaningsih, Riani Putri Dwi Sundari Putri, Aldila Rahma Putri, Ava Emalia Selviana Putri, Karisma Anisa Rachmat, Mudiyono Rahayu, Khatrina Rintis Lintang Rahmad Setiawan Rahmat, Mudiyono Rahmawati, Alfina Pristya Rasulyanti, Amalia Ratih Setiawati RIFAI, MOH. Riska Habriel Ruslie Rivalino, Ricky Robiah Yunus Rodi Wahyudi Rofi, Latifa Hammimatu Rosyida, Dina Safera, Della Dwi Safitri, Tania Saniya, Saniya Sanusi Sanusi Sardulo Gembong, Sardulo Sari Wulandari Satiti, Ihsani Hanif Setyo Septiyaningrum, Fina Dwi Putri Serly, Widya Ambar Setiawan Setiawan Setiawan, Johan Shufyani, Fahma Siahaan, R. Fanry Silowati, Mintut Siti Juariah Siti Mardiana Siti Qomariah, Siti Siti Sarah, Siti Solihin, Dede Solikah, Nurul Islami Solikin Solikin Sri Adi Widodo Sri Wulandari Suadi Zainal sukri Sukri, sukri Suryani, N Lilis Suryaningputri, Dwi Amartani Susanti, Nurdieni Susanto, Noto Sutoro, Moh. Suwondo Suwondo Swasti Maharani, Swasti Syachrofi, Muhammad Syaflita, Dina Syahira, Juniva Syatoto, Iman Syavela, Gea T. G. Chuah T. M. Diansyah Tandana, Ester Taufiq Y.H. Yap Thomas S.Y. Choong Triasroza, Alrohma Nikmawati Trisna Ningsih Turrahmah, Laila Tyas, Nazwa Julia Madyaning Ula, Khayranil Utami, Dhiba Putri Setyari Vera Roni Setiawan Vindi, Yessika Wahyu, Eka Wahyuni, Liya Tri Wan Syafii Wardani, Yulia Nindi Wasilatul Murtafiah Weni Puji Hastuti Wibisono, Putri Sindy Wiwi Sartika Wulandini, Putri Yose Rizal Yulia Yesti, Yulia Yulia, Ruka Yulianti, Lia Mustika Novita Yusmadi, Y Yusrita, Eli Yustina Yustina Zafrida , Siska Zamzam, Zamzam Zulfah Zulfah Zulfarina, Zulfarina