Prevalence of NPHS2 gene R229Q polymorphism in Bangladeshi children with nephrotic syndrome

Sharmin Sultana Jyoti; Farhana Islam; Ishrat Islam Shrabonee; Taposhi Nahid Sultana; Nusrat Islam Chaity; Noor Ahmed Nahid; Md Reazul Islam; Md Saiful Islam; Mohd Nazmul Hasan Apu

doi:10.1016/j.heliyon.2020.e05317

Prevalence of NPHS2 gene R229Q polymorphism in Bangladeshi children with nephrotic syndrome

Heliyon. 2020 Oct 20;6(10):e05317. doi: 10.1016/j.heliyon.2020.e05317. eCollection 2020 Oct.

Authors

Sharmin Sultana Jyoti¹, Farhana Islam¹, Ishrat Islam Shrabonee², Taposhi Nahid Sultana¹, Nusrat Islam Chaity¹, Noor Ahmed Nahid¹, Md Reazul Islam¹, Md Saiful Islam¹, Mohd Nazmul Hasan Apu¹

Affiliations

¹ Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh.
² Department of Pediatric, Mymensingh Medical College Hospital, Mymensingh, 2200, Bangladesh.

Abstract

Background: Limited and contradictory pharmacogenetic studies of NPHS2 gene R229Q polymorphism in nephrotic syndrome (NS) children of different ethnicities steered us to investigate the genotype frequency and associated risk of this polymorphism in Bangladeshi NS children.

Methods: A prospective case-control study was conducted which comprised a total of 142 children having nephrotic syndrome (NS), divided into 2 groups: case group consisted of 40 children with steroid-resistant nephrotic syndrome (SRNS), and control group involved 102 children with steroid-sensitive nephrotic syndrome (SSNS). Both were genotyped by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for R229Q polymorphism.

Results: The results indicate the presence of R229Q polymorphism in 27.50% of SRNS and 12.75% of SSNS children. SRNS children possess 2.94-fold greater risk (p = 0.025) of carrying Arg/Gln genotype compared to SSNS children. Moreover, R229Q variant in SRNS children was observed as in a compound heterozygous form with p.Ala297Val located in exon 8. Age of onset (4-6 years) presents as a significant contributing factor (adjusted OR = 1.06; 95% CI = 1.023-1.094; p = 0.001) for SRNS susceptibility in Bangladeshi children. Contrarily, though the incidence of SRNS was higher in male children than female (80% vs 20%), gender remains to be a neutral factor (p = 0.257) in relation to SRNS susceptibility.

Conclusion: Compound heterozygosity of NPHS2 p.R229Q gene variant with p.Ala297Val may cause pathogenic SRNS in Bangladeshi children. Large scale studies are warranted to establish the genotype-phenotype correlation. It is recommended to screen for p.R229Q first and, if positive, for p.Ala297Val in Bangladeshi SRNS children.

Keywords: Bangladesh; Clinical genetics; Genetic disorders; Human genetics; NPHS2; PCR-RFLP; Pediatrics; R229Q polymorphism; Steroid resistant nephrotic syndrome.