Laboratory of Molecular Cardiology, Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China.
Yunnan Institute of Microbiology, Yunnan University, Kunming, 650091, China.
BMC Med Genet. 2018 Feb 20;19(1):27. doi: 10.1186/s12881-018-0538-4.
Rheumatic heart disease (RHD) is an autoimmune disease triggered by acute rheumatic fever (ARF). Matrix metalloproteinases (MMPs) play an important role in the modulation of immune responses. The purpose of this study was to evaluate the association of MMP1, 3, and 12 promoter polymorphisms with RHD in a Han population in Southern China since the 3 genes are localized on the same chromosome and have a combined effect.
DNA samples were obtained from 90 adult patients with RHD and 90 control subjects. Polymorphisms in MMP1 (rs1799750), MMP3 (rs3025058), and MMP12 (rs2276109) were genotyped by direct sequencing. Differences in genotype and allele frequencies of these polymorphisms were compared between the cases and the controls using Unconditional logistic regression models and Chi-squared test.
The 2G/2G genotype of rs1799750 in MMP1 was associated with a significantly higher risk of RHD when compared with the 1G/1G genotype (OR = 3.227; 95% CI:1.118-9.31; p = 0.03). The frequency of allele 2G was higher in patients with RHD compared to the controls (69.4% vs. 58.9%; p = 0.048) No significant differences in genotype and allele frequencies of rs3025058 in MMP3 and rs2276109 in MMP12 were found between the patients with RHD and the controls (p > 0.05).
Our results suggest that rs1799750 in MMP1 might be a risk factor for RHD in a Han population in Southern China, and individuals carrying the 2G/2G genotype are likely more susceptible to RHD. In contrast, rs3025058 in MMP3 and rs2276109 in MMP12 might not contribute to the risk of developing RHD in this population. Further studies with larger samples and other ethnic populations are required to confirm these findings.
风湿性心脏病（RHD）是由急性风湿热（ARF）引发的自身免疫性疾病。基质金属蛋白酶（MMPs）在调节免疫反应中发挥重要作用。本研究旨在评估 MMP1、3 和 12 启动子多态性与中国南方汉族人群 RHD 的关联，因为这 3 个基因位于同一染色体上且具有协同作用。
从 90 例成年 RHD 患者和 90 例对照中获取 DNA 样本。通过直接测序对 MMP1（rs1799750）、MMP3（rs3025058）和 MMP12（rs2276109）的多态性进行基因分型。采用非条件逻辑回归模型和卡方检验比较病例组和对照组之间这些多态性的基因型和等位基因频率差异。
与 MMP1 的 rs1799750 的 1G/1G 基因型相比，2G/2G 基因型显著增加了 RHD 的发病风险（OR=3.227；95%CI：1.118-9.31；p=0.03）。RHD 患者的等位基因 2G 频率高于对照组（69.4%比 58.9%；p=0.048）。在 MMP3 的 rs3025058 和 MMP12 的 rs2276109 中，病例组和对照组之间的基因型和等位基因频率无显著差异（p>0.05）。
我们的研究结果表明，MMP1 的 rs1799750 可能是中国南方汉族人群 RHD 的一个危险因素，携带 2G/2G 基因型的个体更易患 RHD。相比之下，MMP3 的 rs3025058 和 MMP12 的 rs2276109 可能不会增加该人群患 RHD 的风险。需要进一步进行更大样本量和其他种族人群的研究来证实这些发现。
