Sains Malaysiana 55(10)(2026): 1735-1745

http://doi.org/10.17576/jsm-2026-5510-12

 

IRF6 and SATB2 Polymorphisms in Non-Syndromic Orofacial Clefts among Bangladeshi Patients

(Polimorfisme IRF6 dan SATB2 pada Klef Orofasial Bukan Sindrom dalam kalangan Pesakit Bangladesh)

 

NURUL SYAZANA MOHAMAD SHAH^1,*, NORHAYATI MOHD NOOR¹, WAN AZMAN WAN SULAIMAN¹, SARINA SULONG², AHMAD SUKARI HALIM¹ & MD GOLAM MOSTOFA³

 

¹Department of Plastic Surgery and Reconstructive Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia

²Department of Medical Genetics, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia

³Dhaka Community Hospital, Dhaka, Bangladesh

 

Received: 16 December 2024/Accepted: 2 October 2026

 

*Corresponding author; email: syazanashah@usm.my

 

Abstract

Non-syndromic cleft lip and/or palate (NSCL/P) is a common congenital craniofacial anomaly resulting from the complex interaction of genetic and environmental factors. Although several genetic variants have been associated with NSCL/P, population-specific evidence from Bangladesh remains limited. Therefore, this study aimed to describe the demographic characteristics of Bangladeshi patients with NSCL/P and to investigate the distribution of selected single nucleotide polymorphisms (SNPs) in interferon regulatory factor 6 (IRF6) and special AT-rich sequence-binding protein 2 (SATB2) among patients with NSCL/P and a control group. Sixty-one parents or guardians of patients with NSCL/P were interviewed regarding demographic characteristics, socioeconomic background and family history of cleft.  Dried blood spot (DBS) samples were collected, and genomic DNA was extracted using the QIAamp DNA Micro Kit (Qiagen). Five SNPs in IRF6 (rs2235377, rs2235373, rs2235371, rs861019, and rs2013162) and two SNPs in SATB2 (rs142825652 and rs137853127) were genotyped using TaqMan®-based assays. Allele and genotype frequencies were determined using TaqMan Genotyper software. Fisher’s exact test and odds ratios (ORs) were used to evaluate the distribution of the selected variants between the NSCL/P and control groups. From the total of 61 patients, 84% of the cleft patients were males and 16% were females with a ratio 5:1. All patients were reported to be from low socioeconomic background and claimed no family history of cleft incidence. For IRF6 rs2235377, the C allele frequency was 0.64 in the NSCL/P group compared with 0.53 in the control group (OR = 1.57, P = 0.33). For rs2013162, the A and C alleles occurred at equal frequencies in the NSCL/P group (0.50 each), whereas the C allele was more frequent in the control group (0.58). The remaining IRF6 variants showed no statistically significant differences in allele frequencies between groups (P > 0.05). Both SATB2 SNPs showed identical allele frequencies between the NSCL/P and control groups, with the G allele observed at a frequency of 1.00 in both groups. Male patients and UCL were predominant among the Bangladeshi patients studied. Selected IRF6 SNPs showed differences in genotype distribution, but no significant allele-level association was observed, while the SATB2 variants were not associated with NSCL/P. Despite the limited sample size, this study provides preliminary population-specific data on cleft characteristics and genetic variation in Bangladesh, which may support future genetic studies and improve understanding of NSCL/P in this population. Larger sample size is needed to validate these findings.

Keywords: Bangladeshi; cleft lip and/or palate; gene; IRF6; non-syndromic

 

Abstrak

Klef bibir dan/atau lelangit tanpa sindrom (NSCL/P) merupakan anomali kraniofasial kongenital yang lazim dan berpunca daripada interaksi kompleks antara faktor genetik dan persekitaran. Walaupun beberapa varian genetik telah dikaitkan dengan NSCL/P, bukti populasi khusus dari Bangladesh masih terhad. Oleh itu, kajian ini bertujuan untuk menerangkan ciri demografi pesakit NSCL/P Bangladesh serta mengkaji taburan polimorfisme nukleotida tunggal (SNP) terpilih dalam faktor kawalaturan interferon 6 (IRF6) dan jujukan-pengikat protein 2 khusus kaya AT (SATB2) dalam kalangan pesakit NSCL/P dan kumpulan kawalan. Enam puluh satu orang ibu bapa atau penjaga pesakit NSCL/P telah ditemu bual berkaitan ciri demografi, latar belakang sosioekonomi dan sejarah keluarga klef. Sampel darah kering (DBS) dikumpulkan dan DNA genom diekstrak menggunakan QIAamp DNA Micro Kit (Qiagen). Lima SNP dalam IRF6 (rs2235377, rs2235373, rs2235371, rs861019 dan rs2013162) dan dua SNP dalam SATB2 (rs142825652 dan rs137853127) telah digenotip menggunakan kaedah berasaskan TaqMan®. Frekuensi alel dan genotip ditentukan menggunakan perisian TaqMan Genotyper. Ujian tepat Fisher dan nisbah odds (OR) digunakan untuk menilai taburan varian terpilih antara kumpulan NSCL/P dan kumpulan kawalan. Daripada jumlah 61 orang pesakit, 84% pesakit sumbing adalah lelaki manakala 16% adalah perempuan, dengan nisbah 5:1. Kesemua pesakit dilaporkan daripada latar belakang sosioekonomi rendah dan tidak mempunyai sejarah keluarga klef. Bagi SNP IRF6 rs2235377, frekuensi alel C ialah 0.64 dalam kumpulan NSCL/P berbanding 0.53 dalam kumpulan kawalan (OR = 1.57, P = 0.33). Bagi rs2013162, alel A dan C menunjukkan frekuensi yang sama dalam kumpulan NSCL/P (0.50 setiap satu), manakala alel C lebih kerap dalam kumpulan kawalan (0.58). Varian IRF6 yang lain tidak menunjukkan perbezaan yang signifikan secara statistik dalam frekuensi alel antara kumpulan (P > 0.05). Kedua-dua SNP SATB2 menunjukkan frekuensi alel yang sama antara kumpulan NSCL/P dan kawalan, dengan alel G diperhatikan pada frekuensi 1.00 dalam kedua-dua kumpulan. Pesakit lelaki dan UCL merupakan kumpulan yang paling dominan dalam kalangan pesakit Bangladesh yang dikaji. Walaupun terdapat perbezaan dalam taburan genotip bagi SNP IRF6 terpilih, tiada perkaitan yang signifikan pada aras alel diperhatikan, manakala varian SATB2 yang dikaji tidak menunjukkan perkaitan dengan NSCL/P. Walaupun saiz sampel adalah terhad, kajian ini menyediakan data awal populasi khusus berkaitan ciri klef dan variasi genetik di Bangladesh yang dapat menyokong kajian genetik pada masa hadapan serta meningkatkan pemahaman tentang NSCL/P dalam populasi ini. Kajian dengan saiz sampel yang lebih besar diperlukan untuk mengesahkan penemuan ini.

Kata kunci: Bangladesh; klef bibir dan/atau lelangit; gen; IRF6; tanpa sindrom

 

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