Mehra Rohit, Patra Vikram, Dhillan Rishi, Cvnm Dattatraya, Singh Hemender, Gupta Love, Rastogi Garima, Sharma Indu, Sharma Varun
Department of Vascular and Endovascular Surgery, Command Hospital (Southern Command), Pune, India.
Department of Vascular and Endovascular Surgery, 92-Base Hospital, Jammu, Kashmir, India.
Biol Res. 2025 Mar 19;58(1):17. doi: 10.1186/s40659-025-00599-1.
Varicose veins (VV) are spectrum of common vascular diseases having complex genetic etiology. The Castor Zinc Finger 1 (CASZ1) gene has been involved in vascular development and its variant has shown association with VV in various ethnicities, but CASZ1 susceptibility to VV risk is unexplored in the South Asian Indian population. The objective of this study was to estimate the association of the CASZ1 gene variations and VV susceptibility in the South Asian Indians, and to examine the evolutionary patterns of these variants compared to other populations.
Population based case control analysis was conducted on all CASZ1 variants present in the Global Screening Array, including the established VV variant rs11121615 with a focus on validating and identification of both novel and established genetic markers to capture a full spectrum of population-specific genetic markers unique to studied population group. Linkage disequilibrium patterns and cumulative variant effects were also analyzed, followed by selection pressure assessment using neutrality tests.
Three CASZ1 variants rs72860191 (OR 1.58, 95% CI 1.07-2.32, p = 0.01), rs7519604 (OR 1.43, 95% CI 1.05-1.94, p = 0.01), and rs11121615 (OR 0.69, 95% CI 0.50-0.95, p = 0.02) were observed to be significantly associated with VV. Haplotype analysis identified unique haplotype structure of South Asian Indians compared to other global populations. Moreover, the cumulative OR was observed to be higher than the independently estimated values (OR = 2.41, 95% CI 1.48-3.94), indicating genotypic epistasis of VV associated variants. The neutrality tests revealed balancing selection within CASZ1 in the studied population compared to other populations, CONCLUSION: The present study identified CASZ1 variants and their epistatic interactions is associated with VV susceptibility supported with evidence of balancing selection, provides crucial insights into the genetic architecture of VV in studied group, highlighting the impact of evolutionary forces on disease susceptibility.
静脉曲张（VV）是一类具有复杂遗传病因的常见血管疾病。蓖麻锌指蛋白1（CASZ1）基因参与血管发育，其变异在不同种族中均显示与静脉曲张有关，但在南亚印度人群中，CASZ1对静脉曲张风险的易感性尚未得到研究。本研究的目的是评估南亚印度人群中CASZ1基因变异与静脉曲张易感性的关联，并与其他人群比较，研究这些变异的进化模式。
基于全球筛查阵列中存在的所有CASZ1变异进行群体病例对照分析，包括已确定的静脉曲张变异rs11121615，重点是验证和识别新的及已确定的遗传标记，以获取所研究人群组特有的全谱群体特异性遗传标记。还分析了连锁不平衡模式和累积变异效应，随后使用中性检验进行选择压力评估。
观察到三个CASZ1变异rs72860191（比值比1.58，95%可信区间1.07 - 2.32，p = 0.01）、rs7519604（比值比1.43，95%可信区间1.05 - 1.94，p = 0.01）和rs11121615（比值比0.69，95%可信区间0.50 - 0.95，p = 0.02）与静脉曲张显著相关。单倍型分析确定了南亚印度人与其他全球人群相比独特的单倍型结构。此外，观察到累积比值比高于独立估计值（比值比 = 2.41，95%可信区间1.48 - 3.94），表明静脉曲张相关变异的基因型上位性。中性检验显示，与其他人群相比，所研究人群中CASZ1存在平衡选择。
本研究确定了CASZ1变异及其上位性相互作用与静脉曲张易感性相关，并得到平衡选择证据的支持，为所研究群体中静脉曲张的遗传结构提供了关键见解，突出了进化力量对疾病易感性的影响。
