Association of vitamin D receptor TaqI and ApaI genetic polymorphisms with nephrolithiasis and end stage renal disease: a meta-analysis

Abstract Background The deficiency of vitamin D receptor (VDR) or its ligand, vitamin D3, is linked to the development of renal diseases. The TaqI (rs731236) and ApaI (rs7975232) polymorphisms of VDR gene are widely studied for their association with renal disease risk. However, studies have largely been ambiguous. Methods Meta-analysis was carried out to clarify the association of TaqI (2777 cases and 3522 controls) and ApaI (2440 cases and 3279 controls) polymorphisms with nephrolithiasis (NL), diabetic nephropathy (DN) and end stage renal disease (ESRD). Results The VDR TaqI C-allele under allele contrast was significantly associated with ESRD in both fixed effect and random effect models, and ApaI C-allele with ESRD only under fixed effect model. Cochrane Q-test showed no evidence of heterogeneity for TaqI polymorphism and a significant heterogeneity for Apa I polymorphism. No publication bias was observed for both the polymorphisms. Conclusions The present meta-analysis identifies TaqI and ApaI polymorphisms of VDR gene as risk factors for renal diseases.

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Association of Vitamin D Receptor TaqI and ApaI Genetic Polymorphisms with Nephrolithiasis and End Stage Renal Disease: A Meta-Analysis and an Investigation into Latitudinal Effect on Disease Penetrance

10.21203/rs.2.15511/v1 ◽

2019 ◽

Author(s):

Tajamul Hussain ◽

Shaik M. Naushad ◽

Anwar Ahmed ◽

Salman Alamery ◽

Arif A. Mohammed ◽

...

Keyword(s):

Vitamin D ◽

Renal Disease ◽

End Stage Renal Disease ◽

Disease Risk ◽

Meta Analysis ◽

Renal Diseases ◽

Vdr Gene ◽

Disease Penetrance ◽

Stage Renal Disease ◽

End Stage

Abstract Background: The deficiency of vitamin D receptor (VDR) or its ligand, vitamin D3, is linked to the development of renal diseases. The TaqI (rs731236) and ApaI (rs7975232) polymorphisms of VDR gene are widely studied for their association with renal disease risk. However, studies have largely been ambiguous. Objectives: Here, a meta-analysis comprising 2669 renal disease cases and 3342 controls was carried out to clarify the association of TaqI and ApaI polymorphisms with nephrolithiasis (NL), diabetic nephropathy (DN) and end stage renal disease (ESRD). Methods and Results: The VDR TaqI C-allele under allele contrast and fixed effect models was significantly associated with NL and ESRD, and Apal T-allele with ESRD only under fixed effect model. Cochrane Q-test showed no evidence of heterogeneity for TaqI polymorphism and a significant heterogeneity for Apa I polymorphism. No publication bias was observed for both the polymorphisms. Interestingly, increased disease penetrance with an increase in latitude from south to north across the globe was found only in the case of Taql polymorphism but not with Apal. Conclusions and Implications: The present meta-analysis identifies TaqI and ApaI polymorphisms of VDR gene as significant risk factors for renal diseases. Besides, increased disease penetrance with Taql polymorphism from south to north may corroborate with combined effect of defective VDR expression and decreased vitamin D synthesis due shorter durations of sun exposure with increasing latitude. On the other hand, possibility of Apal polymorphism in linkage disequilibrium with an adjacent functional polymorphism and lack of their co-segregation may have resulted in reduced disease penetrance. Present findings may have implications in understanding the role of gene-environmental interaction in renal disease risk.

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