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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 A.A Sagung Ika Nuriska A.A.Gde Budhiarta Agus Santosa Ake, Anselmus Anak Agung Gde Budhiarta Anak Agung Gde Budhiarta Anak Agung Gede Ari Nanda Bhaswara Anak Agung Gede Budhiarta Anak Agung Gede Mahaindra Putra Andika Budiartha, Putu Gede Azizah, Norma Nur Azizah Bondan Winarno Budhiarta, Anak Agung Gde Budi Ratna Aryani David Dharmawan Harjanto Devinta, Made Ratih Santi Dewa Ayu Sri Agung Suandewi Dewi, Putu Feby Miswari Dumilah Ayuningtyas Eti Kurniaty Gautama M, Putu Gizha Satrya Gede Agung Widya Iswara Gede Andrewartha Gozali, Theodorus Onesiforus Herawati Sudoyo I Gde Raka Widiana I Gde Suranaya Pandit I Gusti Ayu Sri Mahendra Dewi I Gusti Ngurah Kade Mahardika I Gusti Putu Suka Aryana I Ketut Suastika I Ketut Sustika I Made Ady Wirawan I Made Bagiada I Made Pande Dwipayana I Made Siswadi Semadi I Made Siswadi Semadi I Made Siswadi Semadi I Made Yoga Prabawa I Wayan Eka Satriawibawa I Wayan Hartadi Noor I Wayan Losen Adnyana I Wayan Putu Sutirta Yasa I Wayan Sudhana I Wayan Sumardika I. K. Suastika Ida Bagus Aditya Nugraha Ida Bagus Yorky Brahmantya Isabella Soerjanto Putri K Suastika Kadek Dina Puspitasari Kartadinata, Sarah Levina Katrin Wilentina Siahaan Ketut Suega Komang Agus Wira Nugraha Laksmi, Putu Pradnyasanti Made Ayu Devi Pita Loka Made Yogi Krisnanda Malik, Safarina G. Marisye Christantia Mayura, I Gusti Ngurah Mochtar, Fransiska Muhammad Aris Sugiharso Ni Ketut Rai Purnami Ni Luh Made Novi Ratnasari Ni Luh Putri Kresnasari Ni Made Sintia Anggia Sari Nym Astika Nyoman Arya Shridewi Abhigamika Oktavianthi, Suksma Pande Ayu Naya Kasih Permatananda Parastan, Rovie Hikari Prichilia Sarah Permadi R. Prawira Bayu Putra Dewa Ratih Pradnyandari Pemayun Rena, Ni Made Renny Anggreni Rheza Priyadi Rooseno, Ratna Rayeni Natasha Rusditha, Sarah - S., Hantono Safarina G. Malik Saraswati, Putu Ayu Indah Savitri, Putu Dian Hermawati Sari Sukma Oktavianthi Surya Sanjaya Funistera Susy Purnawati Tuty Kuswardani Wan Muhamad Syafiq Wardana, Rr. Cattleya Allayka Wimpie I Pangkahila Wira Gotera ¬Ni Putu Ade Tiwi Tyastarini Tyastarini