Association of vitamin D receptor gene polymorphisms and risk of urolithiasis: results of a genetic epidemiology study a
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ORIGINAL PAPER
Association of vitamin D receptor gene polymorphisms and risk of urolithiasis: results of a genetic epidemiology study and comprehensive meta‑analysis Ali Amar1 · Ayesha Afzal1 · Syed Atif Hussain2 · Athar Hameed3 · Abdul Rafay Khan4 · Madiha Shakoor1 · Aiysha Abid4 · Shagufta Khaliq1 Received: 30 April 2019 / Accepted: 2 September 2019 © Springer-Verlag GmbH Germany, part of Springer Nature 2019
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
Introduction Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00240-019-01157-7) contains supplementary material, which is available to authorized users. * Shagufta Khaliq [email protected] 1
Department of Human Genetics and Molecular Biology, University of Health Sciences, Khayaban‑e‑Jamia Punjab, Lahore 54600, Pakistan
2
Department of Urology, Sheikh Zayed Medical College Hospital, Rahim Yar Khan, Pakistan
3
Department of Urology, Fatima Jinnah Medical University, Lahore, Pakistan
4
Centre for Human Genetics and Molecular Medicine, Sindh Institute of Urology and Transplantation, Karachi, Pakistan
Most common diseases (such as urolithiasis) are complex genetic traits with interplay of both genetic and environmental risk factors towar
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