Jyoti Sharmin Sultana, Islam Farhana, Shrabonee Ishrat Islam, Sultana Taposhi Nahid, Chaity Nusrat Islam, Nahid Noor Ahmed, Islam Md Reazul, Islam Md Saiful, Apu Mohd Nazmul Hasan
Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh.
Department of Pediatric, Mymensingh Medical College Hospital, Mymensingh, 2200, Bangladesh.
Heliyon. 2020 Oct 20;6(10):e05317. doi: 10.1016/j.heliyon.2020.e05317. eCollection 2020 Oct.
Limited and contradictory pharmacogenetic studies of 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.
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.
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.
Compound heterozygosity of 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.
针对不同种族肾病综合征（NS）患儿的基因R229Q多态性进行的药物遗传学研究有限且相互矛盾，这促使我们去调查孟加拉国NS患儿中该多态性的基因型频率及相关风险。
开展了一项前瞻性病例对照研究，共有142名肾病综合征（NS）患儿参与，分为两组：病例组由40名激素抵抗型肾病综合征（SRNS）患儿组成，对照组包含102名激素敏感型肾病综合征（SSNS）患儿。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对两组患儿进行R229Q多态性基因分型。
结果表明，27.50%的SRNS患儿和12.75%的SSNS患儿存在R229Q多态性。与SSNS患儿相比，SRNS患儿携带Arg/Gln基因型的风险高2.94倍（p = 0.025）。此外，在SRNS患儿中观察到R229Q变异以复合杂合形式存在，且与位于第8外显子的p.Ala297Val共存。发病年龄（4至6岁）是孟加拉国儿童患SRNS易感性的一个重要影响因素（调整后的OR = 1.06；95%CI = 1.023 - 1.094；p = 0.001）。相反，尽管男性患儿中SRNS的发病率高于女性（80%对20%），但性别在SRNS易感性方面仍是一个中性因素（p = 0.257）。
p.R229Q基因变异与p.Ala297Val的复合杂合性可能导致孟加拉国儿童患致病性SRNS。有必要开展大规模研究以建立基因型与表型的相关性。建议对孟加拉国SRNS患儿首先筛查p.R229Q，若结果为阳性，则进一步筛查p.Ala297Val。
