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Journal : Journal of Global Pharma Technology

Single Nucleotide Polymorphisms of Transcription Factor 7-LIKE 2 Gene Expressed Different MRNA Isoforms in the Peripheral Blood Made Ratna Saraswati; I Gusti Ngurah Kade Mahardika; Ketut Suastika; Sukma Oktavianthi; Herawati Sudoyo; Safarina G. Malik
Journal of Global Pharma Technology Volume 10 Issue 07: (2018) July 2018
Publisher : Journal of Global Pharma Technology

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Abstract

Background: Single Nucleotide Polymorphisms (SNPs) of the Transcription Factor 7-Like 2 (TCF7L2) diabetes susceptibility gene were located in the noncoding region. Intronic SNP may play a role in mRNA splicing. This study aimed to elucidate whether SNPs of the TCF7L2 gene expressed different mRNA isoforms in the peripheral blood. Methods: Across sectional study was conducted in Legian Bali. A total of 56 subjects were grouped into carrier of TCF7L2SNPs (28 Balinese age 30-74 years,eitherheterozygote or mutant of the rs12255372 SNP [GT or TT], rs7903146 [CT or TT], and rs10885406 [AG or GG])and wild-type of TCF7L2 (28 matched in age and sex Balinese,rs12255372 [GG], rs7903146 [CC], and rs10885406 [AA])which has been identified in the previous study.In this study, the mRNA isolation was done using LS Trizol reagent (Nitrogen®) and variants of the mRNA isoform in the TCF7L2 gene was identified by reverse transcriptase-polymerase chain reaction (RT-PCR) method, using two pairs of overlapping primer.The first primer PCR products were grouped into Group-A, Group-B, Group-C and Group-D. The second primer PCR products were grouped into Group-a, Group-b, Group-c and Group-d. Oral glucose tolerant test (OGTT) was done to both groups.Blood samples were taken during fasting, at 1 hour and 2 hours after the oralglucose load, for blood glucose, and insulin level measurement. Results: There were seven pairs of the group combination including group A-a, A-c, A-d, C-a, C-c, C-dand D-c, and group C-c was the most commonly found among all subjects in this study (42.3%). Subjects with diabetes risk allele were 2.66 times more likely to express group C-ccompared to subjects without diabetes risk allele of SNPs in the TCF7L2 gene (95%CI 1.24–5.72 p=0.011). Mean response of insulin increment after oral glucose load among group C-c was higher compared with the non-group C-c, 84.63±41.01 vs. 62.02±38.09ng/ml (mean difference 22.61 95%CI 0.41–44.80 p=0.046). However, blood glucose level, fasting insulin, HOMA %B and HOMA IR were similar between the two groups. Conclusion: Variants of TCF7L2 gene expressed different mRNA isoformsin the peripheral blood.Compared to subjects without diabetes risk allele of SNPs in the TCF7L2 gene, subject with diabetes risk allele expressed dominant variant isoform mRNA 2.66 timeshigher.The higherresponse of insulin increment after oral glucosewas observedin the dominant variant which may reflectthe early condition of insulin resistant.Keywords: Diabetes, SNP TCF7L2, isoforms mRNA.
Co-Authors Agik Suprayogi Agus Eka Darwinata Amelia, Ni Kadek Shita Anak Agung Ayu Mirah Adi Anak Agung Gde Oka Dharmayudha Anak Agung Gde Putra ANAK AGUNG NGURAH GEDE DWINA WISESA ANAK AGUNG NGURAH OKA PUJAWAN Anak Agung Sagung Istri Pradnyantari Anak Agung Sagung Kendran Andi Bahtiar Batti Anita Dwi Handayani Bambang Sumiarto Bhaskara, Audrey Febiannya Putri Brigita Galilea Adu Charles Rangga Tabbu Daud Steven Triyomi Hariyanto Dewi, Putu Bulan Sasmita DWI SURYANTO Estry Gusnita Damanik F. S. Wignall Fakhrurrasi Fakhri Fedri Rell G.A.M.K. Dewi Ghina Monita Pramudhita Gusti Ayu Dianti Violentina Gusti Ayu Mayani Kristina Dewi Gusti Ayu Yuniati Kencana Gusti Ngurah Narendra Putra Helen Scott-Orr Herawati Sudoyo Heru Susetya I Dewa Made Sukrama I GBA Purwanda I Gede Eka Chandrawan I Gusti Agung Ayu Suartini I Gusti Kamasan Nyoman Arijana I Gusti Ketut Suarjana I Gusti Ketut Suarjana I Gusti Made Krisna Erawan I Gusti Ngurah Badiwangsa Temaja I GUSTI NGURAH DIBYA PRASETYA I Gusti Ngurah Narendra I Gusti Ngurah Narendra Putra I Gusti Ngurah Narendra Putra I Gusti Ngurah Narendra Putra I Gusti Ngurah Narendra Putra1, I K. Suata I KADEK SAKA WIRYANA I Ketut Berata I Made Bagus Arya Permana Ardiana Putra I Made Kardena I Made Sara Wijana I Made Sukada I MADE SUMA ANTARA I Made Suma Anthara I Nengah Kerta Besung I Nengah Kerta Besung i Nengah Wandia I NYOMAN ADI SURATMA I Nyoman Dibia I NYOMAN MANTIK ASTAWA I Nyoman Suartha I Putu Sudiarta I Wayan Bebas I Wayan Gorda I Wayan Masa Tenaya I wayan Teguh Wibawan I Wayan Wirata I-W.T Wibawan I. B. P. Dwija I. K. Suastika I.A.P. Apsari I.B. Oka Suyasa I.B.K. Suardana Ida Ayu Pasti Apsari Ida Ayu Sri Candra Dewi Ida Ayu Sri Chandra Dewi Ida Bagus Kade Suardana Ida Bagus Komang Ardana Ida Bagus Oka Winaya Indrawati Sendow Inna Narayani K. Subrata K. Wirasandhi Kadek Karang Agustina Kadek Satria Adi Marhendra Ketut Tuti Parwati Merati Ketut Wella Mellisandy Lies Parede Luh Made Sudimartini Lusiana Lasmari Siahaan M.T Suhartono MADE PHARMAWATI MADE RATNA SARASWATI . Made Suma Anthara Maggy Thenawidjaja Suhartono Martien Herna Susanti Melkias Oagay Melkias Oagay Messy Saputri Boru Sembiring N. K. Susilarini N. Sri Budiyanti Nareswari, Ayu Widya Ni Ketut Dias Nursanty Ni Ketut Suwiti Ni Komang Eka Agustiani Ni Luh Made Ika Yulita Sari Hadiprata Ni Luh Putu Agustini Ni Luh Watiniasih Ni Luh Wayan Yulia Mirayanti Ni Made Adi Tarini Ni Made Krisna Dewi Ni Made Rita Krisna Dewi Ni Made Ritha Krisna Dewi Ni Made Ritha Krisna Dewi Ni Made Ritha Krisna Dewi Ni Made Ritha Krisna Dewi2 Ni Made Susilawathi Ni Nengah Dwi Fatmawati Ni Nyoman Sri Budayanti Ni Putu Dian Pertiwi Ni Putu Sriwidyani Nyoman Anandiya Ramaditya Oktryna Hodesi Sibarani Pieter Mbolo Maranata Pipit Dwi Pramesti Pramitasuri, Tjokorda Istri Putri Wiliantari Putu Mei Purnama Dewi R Susanti R.D Soejoedono Raka-Sudewi A. A. Rd Soejoedono Retno Damajanti Soejoedono S Murtini S.K. Widyastuti Safarina G. Malik Sayu Raka Padma Wulan Sari, Sayu Raka Padma Wulan Sri Kayati Widyastuti sri murtini . Sukma Oktavianthi Susilawathi, Ni Made Tania Ria Gunawan TJOK GEDE OKA PEMAYUN Tjokorda Sari Nindhia TRI KOMALA SARI Wibawan IWT Widya Asmara Yan Ramona Yosaphat L.S Kote