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Urolithiasis

pp 1–17 | Cite as

Association of vitamin D receptor gene polymorphisms and risk of urolithiasis: results of a genetic epidemiology study and comprehensive meta-analysis

  • Ali Amar
  • Ayesha Afzal
  • Syed Atif Hussain
  • Athar Hameed
  • Abdul Rafay Khan
  • Madiha Shakoor
  • Aiysha Abid
  • Shagufta KhaliqEmail author
Original Paper
  • 1 Downloads

Abstract

Polymorphisms of vitamin D receptor (VDR) gene have been associated with risk of urolithiasis, but, with inconsistent results and lack data from Pakistani population. Therefore, after including our indigenous study data, a comprehensive meta-analysis was performed to provide an evidence-based estimate of any association between VDR polymorphisms and urolithiasis risk. A total of 483 Pakistani subjects, comprising 235 urolithiasis patients and 248 healthy controls, were genotyped for 6 VDR polymorphisms. Additionally, a systematic literature search with subsequent meta-analysis was conducted and pooled odds ratios (ORs) were used to determine the strength of any existent associations. Trial sequential analysis (TSA) was also performed. Results revealed no significant association of any VDR polymorphism and urolithiasis risk in indigenous Pakistani patients. However, meta-analysis of 29 relevant studies indicated that VDR FokI polymorphism significantly increased the risk of urolithiasis in allelic (f vs. F: OR = 1.13; 95% CI = 1.05–1.22; p ≤ 0.01) and recessive (ff vs. FF + Ff: OR = 1.20; 95% CI = 1.05–1.38; p = 0.01) models with no significant heterogeneity. No associations were evident for VDR ApaI, BsmI and TaqI polymorphic variants and urolithiasis risk after correction for multiple testing. Subgroup analysis by ethnicity suggested significant association for FokI variant among Asians. The TSA results demonstrated that the evidence reflecting association of FokI polymorphism and urolithiasis risk was sufficient and conclusive. In conclusion, this meta-analysis suggests that VDR FokI polymorphism is significantly associated with urolithiasis risk, especially in Asians, whereas ApaI, BsmI and TaqI polymorphisms are not associated.

Keywords

VDR Renal stones SNP Case–control Pakistan 

Notes

Acknowledgements

We thank patients who participated in the study and hospital staff who facilitated the research team in data and sample collection. We also acknowledge the facilities and support provided by university staff.

Funding

This study was funded by Higher Education Commission, Pakistan (Grant no. NRPU#1987).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All the procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Ethical Review Committee for Medical and Biomedical Research, University of Health Sciences, Lahore) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

240_2019_1157_MOESM1_ESM.pdf (2.8 mb)
Supplementary material 1 (PDF 2889 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Human Genetics and Molecular BiologyUniversity of Health SciencesLahorePakistan
  2. 2.Department of UrologySheikh Zayed Medical College HospitalRahim Yar KhanPakistan
  3. 3.Department of UrologyFatima Jinnah Medical UniversityLahorePakistan
  4. 4.Centre for Human Genetics and Molecular MedicineSindh Institute of Urology and TransplantationKarachiPakistan

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