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A Molecular Insight of the Role of PIN-1 Promoter Polymorphism (− 667C > T; rs2233679) in Chronic Kidney Disease Patients with Secondary Hyperparathyroidism

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Indian Journal of Clinical Biochemistry Aims and scope Submit manuscript

Abstract

Murine studies stipulate Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN-1) as a key mediator of PTH mRNA stability and is acknowledged by genome-wide-association-studies as secondary hyperparathyroidism defining trait in chronic kidney disease. Therefore, we hypothesize that molecular variants of the PIN-1 gene might affect the incidence and predisposition to secondary hyperparathyroidism in chronic renal insufficiency. A total of 281 adult participants, including 124 chronic kidney disease patients with secondary hyperparathyroidism and 157 healthy controls, were genotyped using polymerase chain reaction-restriction fragment length polymorphism method to unravel the effects of genetic risk loci (PIN-1 gene; − 667C > T; rs2233679) on the susceptibility to secondary hyperparathyroidism in chronic kidney disease. Suitable descriptive statistics was used for different variables. The genotype (x2: 8.03, 2 d. f. p = 0.0181) and allele distribution (x2: 7.27, 2 d. f. p: 0.007) of the − 667C > T variant differed significantly in cases and controls, with no deviation from Hardy–Weinberg equilibrium in either affected or control group. The observed frequencies of T allele of PIN-1 − 667 C > T SNP was significantly high in CKD-SHPT group compared to control group (52.41% vs. 41.71%; p: 0.0118). TT variant of PIN-1 − 667C > T SNP was associated with increased risk for occurrence of CKD-SHPT in univariate analysis (OR: 4.6, p: 0.0032, 95% CI: 1.66–12.76). Further in multivariate analysis, both TT (OR: 3.84, p: 0.002, 95% CI: 0.79–9.26) and CT + TT (OR: 2.51, p: 0.031, 95% CI: 0.64–8.68) variants were independently associated with increased risk for CKD-SHPT, emphasizing the deleterious effect of minor T allele. Serum PTH, phosphorus levels were significantly high in CT and TT genotypes compared to CC genotype of PIN-1 − 667C > T SNP (p = 0.001). PIN-1 promoter functional SNP (− 667C > T; rs2233679) appeared to be an important genetic determinant in etiopathogenesis of CKD-SHPT and genetic variants of this SNP influences the risk stratification and might serve as a predictive marker. Thus, rs2233679 can be useful for outcome predictions during diagnostic processes.

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Authors and Affiliations

  1. All India Institute of Medical Sciences, Rajkot, Gujarat, India

    Digishaben D. Patel, Deepak Parchwani, Sagar Dholariya & Ragini Singh

  2. GMERS Medical College, Himmatnagar, Gujarat, India

    Uday Vachhani, Pratik Raghavani & Ajay Rajput

  3. SMS Medical College, Jaipur, Rajasthan, India

    Tanishk Parchwani

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  1. Digishaben D. Patel
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  2. Deepak Parchwani
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On behalf of all the contributors I will act as guarantor and will correspond with the journal from this point onward.

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Correspondence to Deepak Parchwani.

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Patel, D.D., Parchwani, D., Vachhani, U. et al. A Molecular Insight of the Role of PIN-1 Promoter Polymorphism (− 667C > T; rs2233679) in Chronic Kidney Disease Patients with Secondary Hyperparathyroidism. Ind J Clin Biochem 37, 319–327 (2022). https://doi.org/10.1007/s12291-021-00997-8

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  • DOI: https://doi.org/10.1007/s12291-021-00997-8

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