胆囊癌(GBC)是胆管癌的一种常见且致命的形式,与预后不良有关。本研究旨在调查某些地理区域GBC高发的遗传因素。尤其是在印度北部和东部地区。本病例对照研究集中在MMP2,一个参与肿瘤进展和转移的基因,作为GBC发病机制的潜在候选者。我们使用Sanger测序扫描了12个SNP的MMP2启动子,并在300个病例和300个对照样品中进行了病例对照研究。我们发现了五个罕见的变体(rs1961998763,rs1961996235,rs1391392808,rs1488656253和rs17859816)和一个非多态性SNP(rs17859817)。我们的结果揭示了GBC和MMP2启动子SNP之间的显著关联,rs243865(等位基因-P调整=0.0353)和g.55477735G>A(等位基因-P调整=9.22E-05)。此外,单倍型“C-C-A-C-C”与GBC显著相关(P=4.23E-05)。GBC患者组织样本中变异rs243865的基因型-表型相关性,确定“T”风险等位基因携带者具有较高的MMP2表达水平。此外,HEK293T细胞中的荧光素酶报告基因测定揭示了rs243865变体等位基因\'T\'在MMP2表达中的可能调节作用。我们的研究揭示了MMP2启动子SNP与GBC的关联及其在调节其表达中的作用。
Gallbladder cancer (GBC) is a prevalent and deadly form of bile duct cancer, associated with poor prognosis. This study aimed to investigate the genetic factors contributing to the high incidence of GBC in certain geographical regions, particularly in the Northern and Eastern parts of India. The present
case-control study focused on MMP2, a gene involved in tumor progression and metastasis, as a potential candidate in GBC pathogenesis. We scanned MMP2 promoter for twelve SNPs using Sanger\'s sequencing and carried out a
case-control study in 300 cases and 300 control samples. We found five rare variants (rs1961998763, rs1961996235, rs1391392808, rs1488656253, and rs17859816) and one nonpolymorphic SNP (rs17859817). Our results revealed a significant association between GBC and MMP2 promoter SNPs, rs243865 (Allelic-Padjusted = 0.0353) and g.55477735G > A (Allelic-Padjusted = 9.22E-05). Moreover, the haplotype \"C-C-A-C-C\" exhibited a significant association with GBC (P = 4.23E-05). Genotype-phenotype correlation for variant rs243865, in the GBC patient tissue samples, established that \'T\' risk allele carriers had higher expression levels of MMP2. Additionally, luciferase reporter assay in HEK293T cells revealed the probable regulatory role of rs243865 variant allele \'T\' in MMP2 expression. Our study uncovers the association of MMP2 promoter SNPs with GBC and their role in regulating its expression.