Sains Malaysiana 49(11)(2020): 2755-2761

http://dx.doi.org/10.17576/jsm-2020-4911-14

Association of STAT4 rs7574865 with Sysceptibility to Juvenile Onset Systemic Lupus Erythematous in Pakistani Population

(Perkaitan STAT4 rs7574865 dengan Kebolehlihatan terhadap Penyakit Lupus Erythematous Sistemik Juvenil pada Penduduk Pakistan)

BASHIR RASHEEDA¹*, ALI HIRA¹, MALIK SAIRA², MUNIR NEELMA¹, HAQ RUKHAMA¹, NAZ SHAGUFTA¹ & ALTAF IMRAN³

¹Department of Biotechnology, Lahore College for Women University, Lahore, Pakistan

²Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore, Pakistan

³Institute of Microbiology, University of Veterinary and Animal Sciences, Lahore, Pakistan

Received: 30 October 2019/Accepted: 10 June 2020

ABSTRACT

Association of STAT4 (signal transducer and activator of transcription4) haplotype tagged by single nucleotide polymorphism (SNP) rs7574865 with systemic lupus erythematosus (SLE) was reported in different populations. This study was aimed to investigate a genetic association between STAT4 single nucleotide polymorphism (rs7574865) with susceptibility and clinical features of systemic lupus erythematosus in Pakistani population. A total of 75 clinically diagnosed individuals affected with SLE were enrolled from Children’s Hospital and Institute of Child Health Lahore.  Sixty-eight healthy individuals of same ethnicity were also enrolled for this study. Clinical assessment of patients was done with the help of clinical features suggestive for SLE and some diagnostic tests specific for the disease were performed. SNP rs7574865 was genotyped by allele specific tetra ARMS PCR assay to check and compare the genotypic allele frequencies between SLE patients and healthy controls. Different statistical analysis ChiSquare, Fisher’s exact tests and binary Logistic Regression is performed to determine association of risk alleles with SLE in Pakistani population. p value less than >0.05 consider significant. This study showed the frequency of GG (28%), TT (12%), and GT alleles (60%) in SLE patients while controls showed allele frequencies of GG (5%), TT (29%) and GT (64%), respectively. The results showed that GG genotype and G allele in STAT4 rs7574865 was the risk allele for SLE while T allele proved to be the protective one for disease susceptibility when compared with healthy controls genotypic frequencies. This study suggests the strong association of SNP rs7574865 in STAT4 with the risk of SLE in Pakistani population. However, G allele showed no association with organ damage and immune disorder of SLE.

Keywords: Single nucleotide polymorphism; STAT4; systemic lupus erythematosus

ABSTRAK

Perkaitan antara STAT4 (transduser isyarat dan pengaktif transkripsi4) haplotip bertanda oleh polimorfisme nukleotida tunggal (SNP) rs7574865 dengan lupus eritematosus sistemik (SLE) dilaporkan dalam populasi berbeza. Kajian ini bertujuan untuk mengkaji hubungan genetik antara polimorfisme nukleotida tunggal STAT4 (rs7574865) dengan kerentanan dan ciri klinikal lupus eritematosus sistemik dalam populasi Pakistan. Seramai 75 individu yang didiagnosis secara klinikal terkesan oleh SLE telah didaftarkan dari Hospital Kanak-kanak dan Institut Kesihatan Kanak-kanak Lahore. Enam puluh lapan individu sihat daripada etnik yang sama juga telah didaftarkan untuk kajian ini. Penilaian klinikal pesakit dilakukan dengan bantuan ciri klinikal untuk SLE dan beberapa ujian diagnostik khusus untuk penyakit tersebut dijalankan. SNP rs7574865 digenotip dengan alel khusus tetra asai ARMS PCR untuk menyemak dan membandingkan frekuensi alel genotip antara pesakit SLE dan kawalan sihat. Analisis statistik ChiSquare berbeza, ujian tepat Fisher dan Regresi Logistik binari dijalankan untuk menentukan hubungan risiko alel dengan SLE dalam populasi Pakistan. Nilai p kurang daripada >0.05 dianggap signifikan. Kajian ini menunjukkan frekuensi alel GG (28%), TT (12%) dan GT (60%) pada pesakit SLE sementara kawalan menunjukkan frekuensi alel GG (5%), TT (29%) dan GT (64%). Hasil kajian menunjukkan bahawa genotip GG dan alel G pada STAT4 rs7574865 adalah alel risiko untuk SLE sementara alel T terbukti menjadi pelindung bagi kerentanan penyakit apabila dibandingkan dengan frekuensi genotipik kawalan sihat. Kajian ini mencadangkan perkaitan yang kuat oleh SNP rs7574865 dalam STAT4 dengan risiko SLE dalam populasi Pakistan. Walau bagaimanapun, alel G tidak menunjukkan kaitan dengan kerosakan organ dan gangguan imun SLE.

Kata kunci: Lupus eritematosus sistemik; polimorfisme nukleotida tunggal; STAT4

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*Corresponding author; email: rashidasbs@yahoo.com