ACE I/D Gene Polymorphism Can't Predict the Steroid Responsiveness in Asian Children with Idiopathic Nephrotic Syndrome: A Meta-Analysis

Background: Studies have identified that MIF -173 G>C gene polymorphism is associated with idiopathic nephrotic syndrome (INS) susceptibility and steroid resistance, but the results remain inconclusive.Methods: We searched PubMed, Embase, and Web of Science for relevant studies published before 31 March 2021. Pooled data were reported as odds ratio (OR) with 95% confidence interval (CI). Noteworthiness of significant OR was estimated by the false positive report probability (FPRP) test. Trial sequential analysis (TSA) was used to control type I and type II errors.Results: We selected seven case-control studies that included 1,026 INS children (362 were steroid-resistant NS and 564 were steroid-sensitive NS) and 870 controls. The results showed that MIF -173 G>C polymorphism was significantly associated with INS susceptibility in allelic, heterozygous and dominant genetic models (C vs. G: OR = 1.325, 95% CI: 1.011-1.738; GC vs. GG: OR = 1.540, 95% CI: 1.249-1.899; CC + GC vs. GG: OR = 1.507, 95% CI: 1.231-1.845), and FPRP test and TSA indicated that the associations were true in heterozygous and dominant models. The pooled results also revealed that MIF -173 G>C polymorphism was significantly associated with steroid resistance in allelic, homozygous and recessive models (C vs. G: OR = 1.707, 95% CI: 1.013-2.876; CC vs. GG: OR = 4.789, 95% CI: 2.109-10.877; CC vs. GC + GG: OR = 4.188, 95% CI: 1.831-9.578), but FPRP test indicated that all these associations were not noteworthy. Furthermore, TSA revealed that the non-significant associations between MIF -173 G>C polymorphism and steroid resistance in heterozygous and dominant models were potential false negative.Conclusions: This meta-analysis could draw a firm conclusion that MIF -173 G>C polymorphism was significantly associated with increased INS risk in heterozygous and dominant genetic models. MIF -173 G>C polymorphism was not likely to affect steroid responsiveness, but more studies were needed to confirm.

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Association of angiotensin converting enzyme insertion/deletion gene polymorphism with idiopathic nephrotic syndrome susceptibility in children: a meta-analysis

Journal of the Renin-Angiotensin-Aldosterone System ◽

10.1177/1470320311422578 ◽

2011 ◽

Vol 12 (4) ◽

pp. 601-610 ◽

Cited By ~ 23

Author(s):

Tian-Biao Zhou ◽

Chao Ou ◽

Yuan-Han Qin ◽

Li-Na Su ◽

Feng-Ying Lei ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Gene Polymorphism ◽

Angiotensin Converting Enzyme ◽

Idiopathic Nephrotic Syndrome ◽

Meta Analysis ◽

Positive Association ◽

Converting Enzyme ◽

Positive Role ◽

Different Populations ◽

Search And Selection

Background and objective: Angiotensin converting enzyme (ACE) gene contains either an insertion (I) allele or a deletion (D) allele forming three potential genotypes: II, ID and DD. The D allele or DD genotype has been reported to be associated with higher plasma ACE level. An assessment of the association between ACE I/D gene polymorphism and idiopathic nephrotic syndrome (INS) susceptibility in children is still controversial. This meta-analysis was performed to evaluate the association between ACE I/D gene polymorphism and the onset of INS. Method: A predefined literature search and selection of eligible relevant studies were performed to collect data from electronic databases, and eligible investigations were synthesized using the meta-analysis method. Results: Nine investigations were identified for the analysis of association between ACE I/D gene polymorphism and INS risk in children, including six in Asians, one study for Caucasians and two for Africans. There was positive association between D allele or DD genotype and INS susceptibility in Asians (OR = 1.75, p = 0.01; OR = 2.01, p = 0.02), but not for Caucasian children and Africans (for Caucasians, D: OR=1.35, p = 0.27, DD: OR = 0.95, p = 0.91; for Africans, D: OR = 1.70, p = 0.56, DD: OR = 1.60, p = 0.73). Furthermore, II homozygous seemed to play a positive role against INS onset for Asians (OR = 0.59, p = 0.02), but the link between II genotype and INS risk was not observed in Caucasian children and Africans (Caucasians: OR = 0.31, p = 0.06; Africans: OR = 0.50, p = 0.59). Conclusions: D allele and DD homozygous might become significant genetic molecular markers for INS susceptibility in Asian children, but the association was not observed in Caucasians or Africans. However, the conclusion from our study cannot be sustained and more investigations on larger sample in different populations are required to further clarify the role of D allele or DD homozygous in the onset of INS in difference races.

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