Raina Jyotdeep Kour, Sharma Minakashee, Sharma Ravi, Bhardwaj Rohit, Kumar Parvinder, Banerjee Santasree, Panjaliya Rakesh Kumar
Department of Human Genetics, Government Gandhi Memorial Science College, Cluster University of Jammu, Jammu & Kashmir, Jammu, 180016, India.
Institute of Human Genetics, University of Jammu, Jammu & Kashmir, Jammu, 180016, India.
Orphanet J Rare Dis. 2025 May 14;20(1):229. doi: 10.1186/s13023-025-03761-w.
The activity of SLC6A4 is influenced by its polymorphisms, including the length variation in serotonin transporter linked promoter region (5-HTTLPR), a single nucleotide polymorphism (rs25531), and variable number of tandem repeats in serotonin transporter intronic enhancer (STin2). These polymorphisms have been implicated in the development of vascular diseases. Our research aimed to determine whether the bi-allelic 5-HTTLPR, tri-allelic 5-HTTLPR (rs25531), and STin2 polymorphisms of SLC6A4 were associated with an increased risk of coronary artery disease (CAD) in the North Indian population of Jammu region in Jammu and Kashmir state of India.
In this study, we performed a large cohort case-control study. Here, we recruited 400 patients clinically diagnosed with CAD, and 400 unrelated healthy individuals with similar sex and age range. We performed Polymerase Chain Reaction (PCR) for genotyping the 5-HTTLPR and STin2 polymorphisms. In addition, PCR- Restriction Fragment Length polymorphism (RFLP) was used to perform restriction fragment length polymorphism for the rs25531. Finally, we performed statistical analysis with the yield data.
The L-allele of 5-HTTLPR was significantly associated with CAD susceptibility, with an odd ratio (OR) of 1.39 and a p-value of 0.01. However, no significant association was identified for the tri-allelic 5-HTTLPR (rs25531) and STin2 polymorphism with the susceptibility of CAD. The haplotype combinations associated with CAD outcomes include L-12 and LA-10.
Although, majority of the previous studies have evaluated the association of 5-HTTLPR biallelic polymorphism with CAD, our findings suggested that the tri-allelic 5-HTTLPR (rs25531) is a more reliable candidate than the bi-allelic 5-HTTLPR, as studying the bi-allelic version alone may generate association bias. Based on the results of this study, the rs25531 and STin2 polymorphisms indicated that the SLC6A4 gene does not contribute to the development of CAD in the population of the of Jammu region in Jammu and Kashmir state of India.
SLC6A4的活性受其多态性影响，包括血清素转运体相关启动子区域（5-HTTLPR）的长度变异、单核苷酸多态性（rs25531）以及血清素转运体内含子增强子（STin2）中的串联重复可变数目。这些多态性与血管疾病的发生有关。我们的研究旨在确定SLC6A4的双等位基因5-HTTLPR、三等位基因5-HTTLPR（rs25531）和STin2多态性是否与印度查谟和克什米尔邦查谟地区北印度人群冠状动脉疾病（CAD）风险增加相关。
在本研究中，我们进行了一项大型队列病例对照研究。在此，我们招募了400例临床诊断为CAD的患者以及400名年龄和性别范围相似的无亲缘关系的健康个体。我们进行聚合酶链反应（PCR）对5-HTTLPR和STin2多态性进行基因分型。此外，采用PCR-限制性片段长度多态性（RFLP）对rs25531进行限制性片段长度多态性分析。最后，我们对所得数据进行统计分析。
5-HTTLPR的L等位基因与CAD易感性显著相关，优势比（OR）为1.39，p值为0.01。然而，未发现三等位基因5-HTTLPR（rs25531）和STin2多态性与CAD易感性有显著关联。与CAD结局相关的单倍型组合包括L-12和LA-10。
尽管之前的大多数研究评估了5-HTTLPR双等位基因多态性与CAD的关联，但我们的研究结果表明，三等位基因5-HTTLPR（rs25531）比双等位基因5-HTTLPR更可靠，因为仅研究双等位基因形式可能会产生关联偏差。基于本研究结果，rs25531和STin2多态性表明SLC6A4基因对印度查谟和克什米尔邦查谟地区人群CAD的发生没有影响。
