Mitra Pubali, Maity Biswanath, Pal Dilip Kumar, Das Madhusudan
Department of Zoology, University of Calcutta, West Bengal, India.
Department of Zoology, University of Calcutta, West Bengal, India; Translational Cell Biology Unit, Centre of Biomedical Research; Uttar Pradesh, India.
Urology. 2018 Nov;121:79-85. doi: 10.1016/j.urology.2018.06.033. Epub 2018 Jul 1.
To investigate the potential contribution of parathyroid hormone (PTH) gene polymorphisms in kidney stone disease (KSD), a global clinical problem impacting major burden on public health care system worldwide.
A case-control study was performed in West Bengal (India) with 152 patients reported with calcium-rich stone in kidney and 144 corresponding normal healthy individuals as controls. To identify genetic variants of PTH, the entire coding region, exon-intron boundaries and a few hundred nucleotides downstream the exon 3 (3' UTR region) was bi-directionally sequenced for all the study participants.
Two intronic (rs694 and rs6254) and one synonymous (rs6256, located in exon 3) variant were identified along with 2 single nucleotide polymorphisms (SNPs) (rs307247 and rs307248) in the 3' UTR of the PTH gene. Allele and genotype frequency analysis of these SNPs revealed that rs6254 and rs6256 had moderate association with increased risk of KSD. The 2 SNPs (rs307247 and rs307248) of the 3' UTR, which were in strong linkage disequilibrium, were found to be significantly associated with kidney stone risk in the population of West Bengal, India.
This is the first time report in the world, regarding association of PTH gene polymorphisms with KSD. Our finding suggests that PTH gene polymorphisms can be used as potential genetic markers for early detection of KSD and for preventing its occurrence. Additional studies with larger sample size are essential to validate our result.
肾结石病（KSD）是一个影响全球公共卫生保健系统的全球性临床问题，本研究旨在探讨甲状旁腺激素（PTH）基因多态性在其中的潜在作用。
在印度西孟加拉邦进行了一项病例对照研究，选取152例报告患有富含钙肾结石的患者以及144例相应的正常健康个体作为对照。为了鉴定PTH的基因变异，对所有研究参与者的整个编码区、外显子-内含子边界以及外显子3下游几百个核苷酸（3'UTR区域）进行双向测序。
在PTH基因的3'UTR区域鉴定出两个内含子变异（rs694和rs6254）、一个同义变异（rs6256，位于外显子3）以及两个单核苷酸多态性（SNP）（rs307247和rs307248）。这些SNP的等位基因和基因型频率分析显示，rs6254和rs6256与KSD风险增加具有中度关联。位于3'UTR区域的两个处于强连锁不平衡状态的SNP（rs307247和rs307248），在印度西孟加拉邦人群中被发现与肾结石风险显著相关。
这是世界上首次关于PTH基因多态性与KSD关联的报道。我们的研究结果表明，PTH基因多态性可作为早期检测KSD及预防其发生的潜在遗传标志物。需要更多大样本量的研究来验证我们的结果。
