Balakrishna D, Sowjanya B, Prasad M, Viswakumar R
Department of Biochemistry, Narayana Medical College and Hospital, Chinthareddypalem, Nellore, 524003 Andhra Pradesh India.
Indian J Clin Biochem. 2023 Oct;38(4):485-494. doi: 10.1007/s12291-022-01073-5. Epub 2022 Aug 10.
Coronary artery disease (CAD) is the third foremost reason of death worldwide in both men and women of different age groups, and is associated with 17.8 million mortalities annually due to unknown specific genetic background. Hence, we elucidated the age- and gender-based predisposition of MMP-9 -1562 C > T (rs3918242) genotype and allele frequencies along with serum MMP-9 levels as probable risk factors in the development of CAD. This case-control study comprised 150 CAD patients and 150 controls from the South Indian Population. PCR-RFLP was performed to determine different genotypes of MMP-9 gene and serum levels of MMP-9 were measured using ELISA. Age- and gender-based subgroup analysis was performed to assess the probable risk of genotype-based serum MMP-9 levels. CT heterozygote showed 25.4% increased frequency in overall CAD patients compared to controls (OR, 4.48; p < 0.0001); while it was 29.2% in men patients (OR, 6.68; p < 0.0001). The CT heterozygote incurred 25.2% increased risk of CAD in younger patients (p = 0.0033), and 25.6% in older patients (p = 0.001). Allele frequency analysis revealed 20% increased risk of minor T allele in younger patients (p = 0.001), and was 13% higher compared to older patients (p = 0.04). Patients with CC homozygote and CT heterozygote showed significantly increased serum MMP-9 levels. Further, comparative analysis showed significantly increased MMP-9 serum levels in women with CT heterozygote compared to men with the same genotype. Our findings clearly demonstrated that rs3918242 of MMP-9 gene and high serum levels of MMP-9 are associated with CAD in South Indian population specifically in older women.
The online version contains supplementary material available at 10.1007/s12291-022-01073-5.
冠状动脉疾病(CAD)是全球不同年龄组男性和女性中第三大主要死因,由于未知的特定遗传背景,每年导致1780万人死亡。因此,我们阐明了基质金属蛋白酶-9(MMP-9)-1562 C>T(rs3918242)基因型和等位基因频率以及血清MMP-9水平基于年龄和性别的易感性,将其作为CAD发生的可能危险因素。这项病例对照研究包括150名CAD患者和150名来自南印度人群的对照。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)来确定MMP-9基因的不同基因型,并使用酶联免疫吸附测定(ELISA)测量血清MMP-9水平。进行基于年龄和性别的亚组分析,以评估基于基因型的血清MMP-9水平的可能风险。与对照组相比,CT杂合子在总体CAD患者中的频率增加了25.4%(比值比,4.48;p<0.0001);而在男性患者中为29.2%(比值比,6.68;p<0.0001)。CT杂合子在年轻患者中患CAD的风险增加了25.2%(p=0.0033),在老年患者中增加了25.6%(p=0.001)。等位基因频率分析显示,年轻患者中次要T等位基因的风险增加了20%(p=0.001),比老年患者高13%(p=0.04)。CC纯合子和CT杂合子患者的血清MMP-9水平显著升高。此外,比较分析显示,与具有相同基因型的男性相比,CT杂合子女性的血清MMP-9水平显著升高。我们的研究结果清楚地表明,MMP-9基因的rs3918242和高血清MMP-9水平与南印度人群中的CAD相关,特别是在老年女性中。
在线版本包含可在10.1007/s12291-022-01073-5获取的补充材料。