Dataset Information

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

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.

SUBMITTER: Jyoti SS

PROVIDER: S-EPMC7578689 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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

Jyoti Sharmin Sultana SS Islam Farhana F Shrabonee Ishrat Islam II Sultana Taposhi Nahid TN Chaity Nusrat Islam NI Nahid Noor Ahmed NA Islam Md Reazul MR Islam Md Saiful MS Apu Mohd Nazmul Hasan MNH

Heliyon 20201020 10

<h4>Background</h4>Limited and contradictory pharmacogenetic studies of <i>NPHS2</i> 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.<h4>Methods</h4>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-resist ...[more]

PMID: 33102883

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Project description:BACKGROUND: Nephrotic syndrome is traditionally classified on the basis of the response to standard steroid treatment. Mutations in more than 24 genes have been associated with nephrotic syndrome in children, although the great majority of steroid-resistant cases have been attributed to mutations in three main genes: NPHS1, NPHS2 and WT1. The aims of this study were to identify mutations in these genes more frequently reported as mutated and to characterize each variation using different in silico prediction algorithms in order to understand their biological functions. METHODS: We performed direct sequence analysis of exons 8 and 9 of WT1, 8 exons of NPHS2 and 29 exons of NPHS1, including NPHS2 and NPHS1 intron-exon boundary sequences, as well as 700 bp of the 5' UTR from both genes in 27 steroid-resistant patients aged between 3 months and 18 years. RESULTS: Analysis of the NPHS2 gene revealed four missense mutations, one frameshift mutation and three variations in the 5' UTR. Four patients presented compound heterozygosis, and four other patients presented one heterozygous alteration only. WT1 and NPHS1 gene analysis did not reveal any mutations. DISCUSSION: This is the first study focusing on genetics of SRNS in Brazilian children. Identification of mutations is important because it could influence physicians' decision on patient treatment, as patients carrying mutations can be spared the side effects of immunosuppressive therapy and ultimately could be considered for kidney transplantation from a living donor. CONCLUSIONS: After molecular analysis of the genes more frequently reported as mutated in 27 steroid-resistant nephrotic syndrome patients, we identified NPHS2 mutations confirming the hereditary character of the kidney disease in only 14.8% of patients. Therefore, the next step is to perform a next generation sequencing based analysis of glomeluropathy-related panel of genes for the remaining patients in order to search for mutations in other genes related to steroid-resistant nephrotic syndrome.

Dataset Information

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

Publications

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

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