Sains Malaysiana 52(6)(2023): 1835-1844

http://doi.org/10.17576/jsm-2023-5206-18

Genetic Association Study of STAT4 Polymorphisms and Type 1 Diabetes in Pakistani Children

(Penyelidikan Perkaitan Genetik Polimorfisme STAT4 dan Diabetes Jenis 1 pada Kanak-kanak di Pakistan)

SANA RAFAQAT¹, JAIDA MANZOOR², MARIA ADREES¹, HAFSA HAMID¹, ASIFA KAMAL³ & RASHEEDA BASHIR^1,*

¹Department Of Biotechnology, Lahore College for Women University, 54000, Lahore, Pakistan

²Department Of Endocrinology and Diabetes, The Children's Hospital & University of Child Health Sciences, 54000, Lahore, Pakistan

³Department Of Statistics, Lahore College for Women University, 54000, Lahore, Pakistan

Received: 4 October 2022/Accepted: 6 June 2023

Abstract

The present study investigated the relationship of STAT4 single nucleotide polymorphisms (SNPs) rs7574685, rs10181656, and rs3821236 with T1D susceptibility visiting tertiary care hospital in Lahore, Punjab, Pakistan. One hundred and fifty-five T1D patients and one hundred and five healthy individuals were enrolled. An expert endocrinologist collected the clinical data of T1D patients. The genotyping of three potential STAT4 SNPs was performed through Tetra ARMS-PCR assay. The relationship between SNPs and T1D susceptibility under several genetic models, including dominant, recessive, and codominant models, was assessed by regression analysis. All clinical features of T1D demonstrate a significant difference from control groups (P<0.01) except blindness. The characteristic biochemical analysis determined that participants with T1D had significantly higher fasting blood glucose levels and glycated hemoglobin (HbA1c) levels than the control group (P<0.01). Genetic analysis of rs7574685 depicts GT genotype was found to be the risk allele for the development of T1D when compared to the control group. For rs10181656 and rs3821236, the GC genotype and GA genotype were observed to be the risk alleles in the T1D cases as compared to the control group (P=0.04, P<0.01, respectively). Genetic models showed that the STAT4 GG genotype of rs7574685 in the dominant model (OR=1.73, 95% CI=1.05-2.86), GC genotype of rs10181656 in the codominant model (OR=2.079, 95 % CI=1.16-3.71), and AA genotype of rs3821236 showed significant risk association with T1D (OR=3.486, 95% CI=1.72-7.03). It is concluded that the risk of T1D is highly correlated with the STAT4 variants of rs7574685 and rs10181656 among children of the Pakistani population.

Keywords: Polymorphism; STAT4; T1D; variants

Abstrak

Penyelidikan ini mengkaji hubungan polimorfisme nukleotida tunggal STAT4 (SNP) rs7574685, rs10181656 dan rs3821236 dengan kerentanan T1D yang melawat hospital penjagaan tertiari di Lahore, Punjab, Pakistan. Seratus lima puluh lima pesakit T1D dan seratus lima individu yang sihat telah didaftarkan. Pakar endokrinologi mengumpul data klinikal pesakit T1D. Genotip tiga SNP STAT4 yang berpotensi dilakukan melalui ujian Tetra ARMS-PCR. Hubungan antara SNP dan kerentanan T1D di bawah beberapa model genetik, termasuk model dominan, resesif dan kodominan, telah dinilai oleh analisis regresi. Semua ciri klinikal T1D menunjukkan perbezaan yang ketara daripada kumpulan kawalan (P<0.01) kecuali buta. Analisis biokimia ciri menentukan bahawa peserta dengan T1D mempunyai paras glukosa darah puasa dan paras hemoglobin terglikasi (HbA1c) yang jauh lebih tinggi daripada kumpulan kawalan (P<0.01). Analisis genetik rs7574685 menggambarkan genotip GT didapati sebagai alel risiko untuk pembangunan T1D jika dibandingkan dengan kumpulan kawalan. Untuk rs10181656 dan rs3821236, genotip GC dan genotip GA diperhatikan sebagai alel risiko dalam kes T1D berbanding kumpulan kawalan (P = 0.04, P <0.01, masing-masing). Model genetik menunjukkan bahawa genotip STAT4 GG rs7574685 dalam model dominan (OR=1.73, 95% CI=1.05-2.86), genotip GC rs10181656 dalam model kodominan (OR=2.079, 95% CI=1.16),-3 dan genotip AA rs3821236 menunjukkan perkaitan risiko yang ketara dengan T1D (OR=3.486, 95% CI=1.72-7.03). Disimpulkan bahawa risiko T1D sangat berkorelasi dengan varian STAT4 rs7574685 dan rs10181656 dalam kalangan populasi kanak-kanak Pakistan.

Kata kunci: Polimorfisme; STAT4; T1D; varian

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*Corresponding author; email: rashidasbs@yahoo.com