Relationship Between FKBP5 Polymorphisms at Rs1334894, Rs9394309, and Rs6912833 Loci, and Dyslipidemia in Pediatric Nephrotic Syndrome

Shuting Peng; Fang Yang; Zhiqiang Guo; Ding Liu

doi:doi:10.11648/j.ajp.20230902.13

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Relationship Between FKBP5 Polymorphisms at Rs1334894, Rs9394309, and Rs6912833 Loci, and Dyslipidemia in Pediatric Nephrotic Syndrome

Shuting Peng, Fang Yang, Zhiqiang Guo, Ding Liu

Published in American Journal of Pediatrics (Volume 9, Issue 2)

Received: 9 April 2023 Accepted: 26 April 2023 Published: 10 May 2023

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Abstract

Background: This study aimed to investigate the relationship between rs1334894, rs9394309, and rs6912833 polymorphisms in FKBP5 and hyperlipidemia in nephrotic syndrome (NS). Methods: The case group included 74 children with primary NS, while the control group included 76 healthy children. Polymerase chain reaction and gene sequencing were used to detect polymorphisms at the rs1334894, rs9394309, and rs6912833 loci of FKBP5, in children with NS. Clinical data of total cholesterol (CHOL), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and plasma albumin were collected. Correlations between FKBP5 polymorphisms and serum lipid levels were analyzed during the active period of the disease. Results: A significant difference in LDL levels between the AA and TA genotypes was observed at the rs6912833 locus of FKBP5 in the case group, but no statistical difference in CHOL, TG, and HDL levels between these genotypes was found. No statistically significant differences in LDL levels between the AA and TA genotypes, and among the steroid-sensitive, -dependent, and -resistant groups were noted. Moreover, no statistically significant differences in the CHOL, TG, HDL, and LDL levels were observed between TT and TC genotypes at the rs1334894 locus. Conclusion: The AA genotype at the rs6912833 locus of FKBP5 may be correlated with plasma lipid levels (LDL) in PNS patients.

Published in	American Journal of Pediatrics (Volume 9, Issue 2)
DOI	10.11648/j.ajp.20230902.13
Page(s)	68-74
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Primary Nephrotic Syndrome, FKBP5, Dyslipidemia, Gene Polymorphism

References

[1]	Ordonez JD, Hiatt RA, Killebrew EJ, Fireman BH. The increased risk of coronary heart disease associated with nephrotic syndrome. Kidney Int. 1993; 44: 638–642.
[2]	Moorhead JF, Chan MK, El-Nahas M, Varghese Z. Lipid nephrotoxicity in chronic progressive glomerular and tubulo-interstitial disease. Lancet. 1982; 2: 1309–1311.
[3]	Gyebi L, Soltani Z, Reisin E. Lipid nephrotoxicity: new concept for an old disease. Curr Hypertens Rep. 2012; 14: 177–181.
[4]	Ninomiya T, Kiyohara Y, Kubo M, Yonemoto K, Tanizaki Y, Doi Y, et al. Metabolic syndrome and CKD in a general Japanese population: the Hisayama Study. Am J Kidney Dis. 2006; 48: 383–91.
[5]	Schaeffner ES, Kurth T, Curhan GC, Glynn RJ, Rexrode KM, Baigent C, et al. Cholesterol and the risk of renal dysfunction in apparently healthy men. J Am Soc Nephrol. 2003; 14: 2084–91.
[6]	Appel GB, Blum CB, Chien S, et al. The hyperlipidemia of the nephrotic syndrome: relation to plasma albumin concentration, oncotic pressure and viscosity. N Engl J Med. 1985, 312: 15441-1548.
[7]	Shearer GC, Stevenson FT, Atkinson DN, et al. Hypoalbuminemia and proteinuria contribute separately to reduced lipoprotein catabolism in the nephrotic syndrome. Kidney Int. 2001, 59 (1): 179-189.
[8]	Hu P, Lu L, Hu B, et al. Characteristics of lipid metabolism under different urinary protein excretion in children with primary nephrotic syndrome. Scand J Clin Lab Invest. 2009, 69 (6): 680-6.
[9]	Maria J. Pereira, et al. FKBP5 expression in human adipose tissue increases following dexamethasone exposure and is associated with insulin resistance. Metabolism. 2014, 015: 0026 0495.
[10]	Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Glomerulonephritis. Kidney Int. 2012; 2: 139–274.
[11]	The Subspecialty Group of Nephrology, Society of Pediatrics, Chinese Medical Association. Evidence-based guidelines on diagnosis and treatment of childhood common renal diseases (I) Evidence-bused guideline on diagnosis and treatment of steroid-sensitive, relapsing/steroid-dependent nephrotic syndrome (for trial implementation). Chin J Pediatr. 2009, 047 (003): 167-170.
[12]	The Subspecialty Group of Nephrology, Society of Pediatrics, Chinese Medical Association. Evidence-based guidelines on diagnosis and treatment of childhood common renal diseases (III): Guideline on diagnosis and treatment of steroid-resistant nephrotic syndrome. Chin J Pediatr. 2010, 048 (001): 72-75.
[13]	Warwick GL, Packard CJ, Demant T, et al. Metabolism of apolipoprotein B-containing lipoproteins in subjects with nephrotic-range proteinuria. Kidney Int. 1991; 40: 129–138.
[14]	Warwick GL, Caslake MJ, Boulton-Jones JM, et al. Low-density lipoprotein metabolismin the nephrotic syndrome. Metabolism. 1990; 39: 187–192.
[15]	Greenfield M, Kraemer F, Reaven GM. Relationship between insulin resistance, insulin secretion, very low density lipoprotein kinetics, and plasma triglyceride levels in normotriglyceridemic man. Metabolism. 1981; 30: 165–171.
[16]	Banks WA, Farr SA, Salameh TS, et al. Triglycerides cross the blood-brain barrier and induce central leptin and insulin receptor resistance. Int J Obes (Lond). 2018 Mar; 42 (3): 391–397.
[17]	Klimentidis YC, Arora A. Interaction of Insulin Resistance and Related Genetic Variants with Triglyceride-Associated Genetic Variants. Circ Cardiovasc Genet. 2016 Apr; 9 (2): 154-61.
[18]	Siekierka JJ, Hung S HY, Poe M, et al. A cytosolic binding protein for the immunosuppressant FK506 has peptidyl-prolyl isomerase activity but is distinct from cyclophilin. Nature. 1989, 341 (6244): 755-7.
[19]	Sinars CR, Cheungflynn J, Rimerman RA, et al. Structure of the large FK506-binding protein FKBP51, an Hsp90-binding protein and a component of steroid receptor complexes. Proc Natl Acad Sci U S A. 2003 Feb 4; 100 (3): 868–873.
[20]	Toneatto J, Guber S, Charo N L, et al. Dynamic mitochondrial-nuclear redistribution of the immunophilin FKBP51 is regulated by the PKA signaling pathway to control gene expression during adipocyte differentiation. J Cell Sci. 2013, 126 (23): 5357-68.
[21]	Yang L, Isoda F, Yen K, et al. Hypothalamic Fkbp51 is induced by fasting, and elevated hypothalamic expression promotes obese phenotypes. Am J Physiol Endocrinol Metab. 2012, 302 (8): E987-91.
[22]	Stechschulte LA, Jr HT, Khuder SS, et al. FKBP51 controls cellular adipogenesis through p38 kinase-mediated phosphorylation of GRα and PPAR-γ. Mol Endocrinol. 2014 Aug; 28 (8): 1265–1275.
[23]	Zhang M, Qiu B, Cao Y, Xu YX, Deng R, et al. FKBP51 plays an important role in high fat diet-induced obesity. Chin J Comp Med. 2015 (7).
[24]	Russell LC, Whitt SR, Chen MS, et al. Identification of conserved residues required for the binding of a tetratricopeptide repeat domain to heat shock protein 90. J Biol Chem. 1999, 274 (29): 20060-20063.
[25]	Grad I, Picard D. The glucocorticoid responses are shaped by molecular chaperones. Mol Cell Endocrinol. 2007, 275 (1-2): 2-12.
[26]	Schiene-Fischer C, Yu C. Receptor accessory folding helper enzymes: the functional role of peptidyl prolyl cis/trans isomerases. Febs Lett. 2001, 495 (1): 1-6.
[27]	Westberry JM, Sadosky PW, Hubler TR, et al. Glucocorticoid resistance in squirrel monkeys results from a combination of a transcriptionally incompetent glucocorticoid receptor and overexpression of the glucocorticoid receptor co-chaperone FKBP51. J Steroid Biochem Mol Biol. 2006, 100 (1): 34-41.
[28]	Aouadi M, Jager J, Laurent K, et al. p38MAP Kinase activity is required for human primary adipocyte differentiation. FEBS Lett. 2007 Dec 11; 581 (29): 5591-6.
[29]	Aouadi M, Laurent K, Prot M, et al. Inhibition of p38MAPK increases adipogenesis from embryonic to adult stages. Diabetes. 2006, 55 (2): 281-289.
[30]	Pei H, Li L, Fridley BL, et al. FKBP51 Affects Cancer Cell Response to Chemotherapy by Negatively Regulating Akt. Cancer Cell, 2009, 16 (3): 259-266.
[31]	Hou J, Wang L. FKBP5 as a selection biomarker for gemcitabine and Akt inhibitors in treatment of pancreatic cancer. PloS One. 2012, 7 (5): e36252.
[32]	Fabian AK, März A, Neimanis S, et al. InterAKTions with FKBPs--mutational and pharmacological exploration. PLOS ONE, 2013, 8 (2): e57508.
[33]	Miller AL, Webb MS, Copik AJ, et al. p38 Mitogen-activated protein kinase (MAPK) is a key mediator in glucocorticoid-induced apoptosis of lymphoid cells: correlation between p38 MAPK activation and site-specific phosphorylation of the human glucocorticoid receptor at serine 211 [J]. Mol Endocrinol. 2005, 19 (6): 1569-83.
[34]	Van Wijk JP, De Koning EJ, Martens EP, et al. Thiazolidinediones and blood lipids in type 2 diabetes. Arterioscler Thromb Vasc Biol. 2003, 23 (10): 1744-1749.

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APA Style

Shuting Peng, Fang Yang, Zhiqiang Guo, Ding Liu. (2023). Relationship Between FKBP5 Polymorphisms at Rs1334894, Rs9394309, and Rs6912833 Loci, and Dyslipidemia in Pediatric Nephrotic Syndrome. American Journal of Pediatrics, 9(2), 68-74. https://doi.org/10.11648/j.ajp.20230902.13

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ACS Style

Shuting Peng; Fang Yang; Zhiqiang Guo; Ding Liu. Relationship Between FKBP5 Polymorphisms at Rs1334894, Rs9394309, and Rs6912833 Loci, and Dyslipidemia in Pediatric Nephrotic Syndrome. Am. J. Pediatr. 2023, 9(2), 68-74. doi: 10.11648/j.ajp.20230902.13

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AMA Style

Shuting Peng, Fang Yang, Zhiqiang Guo, Ding Liu. Relationship Between FKBP5 Polymorphisms at Rs1334894, Rs9394309, and Rs6912833 Loci, and Dyslipidemia in Pediatric Nephrotic Syndrome. Am J Pediatr. 2023;9(2):68-74. doi: 10.11648/j.ajp.20230902.13

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@article{10.11648/j.ajp.20230902.13,
  author = {Shuting Peng and Fang Yang and Zhiqiang Guo and Ding Liu},
  title = {Relationship Between FKBP5 Polymorphisms at Rs1334894, Rs9394309, and Rs6912833 Loci, and Dyslipidemia in Pediatric Nephrotic Syndrome},
  journal = {American Journal of Pediatrics},
  volume = {9},
  number = {2},
  pages = {68-74},
  doi = {10.11648/j.ajp.20230902.13},
  url = {https://doi.org/10.11648/j.ajp.20230902.13},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajp.20230902.13},
  abstract = {Background: This study aimed to investigate the relationship between rs1334894, rs9394309, and rs6912833 polymorphisms in FKBP5 and hyperlipidemia in nephrotic syndrome (NS). Methods: The case group included 74 children with primary NS, while the control group included 76 healthy children. Polymerase chain reaction and gene sequencing were used to detect polymorphisms at the rs1334894, rs9394309, and rs6912833 loci of FKBP5, in children with NS. Clinical data of total cholesterol (CHOL), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and plasma albumin were collected. Correlations between FKBP5 polymorphisms and serum lipid levels were analyzed during the active period of the disease. Results: A significant difference in LDL levels between the AA and TA genotypes was observed at the rs6912833 locus of FKBP5 in the case group, but no statistical difference in CHOL, TG, and HDL levels between these genotypes was found. No statistically significant differences in LDL levels between the AA and TA genotypes, and among the steroid-sensitive, -dependent, and -resistant groups were noted. Moreover, no statistically significant differences in the CHOL, TG, HDL, and LDL levels were observed between TT and TC genotypes at the rs1334894 locus. Conclusion: The AA genotype at the rs6912833 locus of FKBP5 may be correlated with plasma lipid levels (LDL) in PNS patients.},
 year = {2023}
}

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TY  - JOUR
T1  - Relationship Between FKBP5 Polymorphisms at Rs1334894, Rs9394309, and Rs6912833 Loci, and Dyslipidemia in Pediatric Nephrotic Syndrome
AU  - Shuting Peng
AU  - Fang Yang
AU  - Zhiqiang Guo
AU  - Ding Liu
Y1  - 2023/05/10
PY  - 2023
N1  - https://doi.org/10.11648/j.ajp.20230902.13
DO  - 10.11648/j.ajp.20230902.13
T2  - American Journal of Pediatrics
JF  - American Journal of Pediatrics
JO  - American Journal of Pediatrics
SP  - 68
EP  - 74
PB  - Science Publishing Group
SN  - 2472-0909
UR  - https://doi.org/10.11648/j.ajp.20230902.13
AB  - Background: This study aimed to investigate the relationship between rs1334894, rs9394309, and rs6912833 polymorphisms in FKBP5 and hyperlipidemia in nephrotic syndrome (NS). Methods: The case group included 74 children with primary NS, while the control group included 76 healthy children. Polymerase chain reaction and gene sequencing were used to detect polymorphisms at the rs1334894, rs9394309, and rs6912833 loci of FKBP5, in children with NS. Clinical data of total cholesterol (CHOL), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and plasma albumin were collected. Correlations between FKBP5 polymorphisms and serum lipid levels were analyzed during the active period of the disease. Results: A significant difference in LDL levels between the AA and TA genotypes was observed at the rs6912833 locus of FKBP5 in the case group, but no statistical difference in CHOL, TG, and HDL levels between these genotypes was found. No statistically significant differences in LDL levels between the AA and TA genotypes, and among the steroid-sensitive, -dependent, and -resistant groups were noted. Moreover, no statistically significant differences in the CHOL, TG, HDL, and LDL levels were observed between TT and TC genotypes at the rs1334894 locus. Conclusion: The AA genotype at the rs6912833 locus of FKBP5 may be correlated with plasma lipid levels (LDL) in PNS patients.
VL  - 9
IS  - 2
ER  -

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Author Information

Shuting Peng

Department of Pediatrics, First Affiliated Hospital of Jinan University, Guangzhou, China
Fang Yang

Department of Pediatrics, First Affiliated Hospital of Jinan University, Guangzhou, China
Zhiqiang Guo

Department of Pediatrics, First Affiliated Hospital of Jinan University, Guangzhou, China
Ding Liu

Department of Pediatrics, First Affiliated Hospital of Jinan University, Guangzhou, China

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APA Style

Shuting Peng, Fang Yang, Zhiqiang Guo, Ding Liu. (2023). Relationship Between FKBP5 Polymorphisms at Rs1334894, Rs9394309, and Rs6912833 Loci, and Dyslipidemia in Pediatric Nephrotic Syndrome. American Journal of Pediatrics, 9(2), 68-74. https://doi.org/10.11648/j.ajp.20230902.13

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ACS Style

Shuting Peng; Fang Yang; Zhiqiang Guo; Ding Liu. Relationship Between FKBP5 Polymorphisms at Rs1334894, Rs9394309, and Rs6912833 Loci, and Dyslipidemia in Pediatric Nephrotic Syndrome. Am. J. Pediatr. 2023, 9(2), 68-74. doi: 10.11648/j.ajp.20230902.13

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AMA Style

Shuting Peng, Fang Yang, Zhiqiang Guo, Ding Liu. Relationship Between FKBP5 Polymorphisms at Rs1334894, Rs9394309, and Rs6912833 Loci, and Dyslipidemia in Pediatric Nephrotic Syndrome. Am J Pediatr. 2023;9(2):68-74. doi: 10.11648/j.ajp.20230902.13

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@article{10.11648/j.ajp.20230902.13,
  author = {Shuting Peng and Fang Yang and Zhiqiang Guo and Ding Liu},
  title = {Relationship Between FKBP5 Polymorphisms at Rs1334894, Rs9394309, and Rs6912833 Loci, and Dyslipidemia in Pediatric Nephrotic Syndrome},
  journal = {American Journal of Pediatrics},
  volume = {9},
  number = {2},
  pages = {68-74},
  doi = {10.11648/j.ajp.20230902.13},
  url = {https://doi.org/10.11648/j.ajp.20230902.13},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajp.20230902.13},
  abstract = {Background: This study aimed to investigate the relationship between rs1334894, rs9394309, and rs6912833 polymorphisms in FKBP5 and hyperlipidemia in nephrotic syndrome (NS). Methods: The case group included 74 children with primary NS, while the control group included 76 healthy children. Polymerase chain reaction and gene sequencing were used to detect polymorphisms at the rs1334894, rs9394309, and rs6912833 loci of FKBP5, in children with NS. Clinical data of total cholesterol (CHOL), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and plasma albumin were collected. Correlations between FKBP5 polymorphisms and serum lipid levels were analyzed during the active period of the disease. Results: A significant difference in LDL levels between the AA and TA genotypes was observed at the rs6912833 locus of FKBP5 in the case group, but no statistical difference in CHOL, TG, and HDL levels between these genotypes was found. No statistically significant differences in LDL levels between the AA and TA genotypes, and among the steroid-sensitive, -dependent, and -resistant groups were noted. Moreover, no statistically significant differences in the CHOL, TG, HDL, and LDL levels were observed between TT and TC genotypes at the rs1334894 locus. Conclusion: The AA genotype at the rs6912833 locus of FKBP5 may be correlated with plasma lipid levels (LDL) in PNS patients.},
 year = {2023}
}

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TY  - JOUR
T1  - Relationship Between FKBP5 Polymorphisms at Rs1334894, Rs9394309, and Rs6912833 Loci, and Dyslipidemia in Pediatric Nephrotic Syndrome
AU  - Shuting Peng
AU  - Fang Yang
AU  - Zhiqiang Guo
AU  - Ding Liu
Y1  - 2023/05/10
PY  - 2023
N1  - https://doi.org/10.11648/j.ajp.20230902.13
DO  - 10.11648/j.ajp.20230902.13
T2  - American Journal of Pediatrics
JF  - American Journal of Pediatrics
JO  - American Journal of Pediatrics
SP  - 68
EP  - 74
PB  - Science Publishing Group
SN  - 2472-0909
UR  - https://doi.org/10.11648/j.ajp.20230902.13
AB  - Background: This study aimed to investigate the relationship between rs1334894, rs9394309, and rs6912833 polymorphisms in FKBP5 and hyperlipidemia in nephrotic syndrome (NS). Methods: The case group included 74 children with primary NS, while the control group included 76 healthy children. Polymerase chain reaction and gene sequencing were used to detect polymorphisms at the rs1334894, rs9394309, and rs6912833 loci of FKBP5, in children with NS. Clinical data of total cholesterol (CHOL), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and plasma albumin were collected. Correlations between FKBP5 polymorphisms and serum lipid levels were analyzed during the active period of the disease. Results: A significant difference in LDL levels between the AA and TA genotypes was observed at the rs6912833 locus of FKBP5 in the case group, but no statistical difference in CHOL, TG, and HDL levels between these genotypes was found. No statistically significant differences in LDL levels between the AA and TA genotypes, and among the steroid-sensitive, -dependent, and -resistant groups were noted. Moreover, no statistically significant differences in the CHOL, TG, HDL, and LDL levels were observed between TT and TC genotypes at the rs1334894 locus. Conclusion: The AA genotype at the rs6912833 locus of FKBP5 may be correlated with plasma lipid levels (LDL) in PNS patients.
VL  - 9
IS  - 2
ER  -

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