School of Medicine, NanKai University, Weijin Road No. 94, Nankai District, 300071, Tianjin, China.
Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin Eye Hospital, Gansu Road No. 4, Heping District, 300020, Tianjin, China.
BMC Endocr Disord. 2021 Sep 30;21(1):195. doi: 10.1186/s12902-021-00837-z.
The serine protease inhibitor-1 (SERPINE1) rs1799889 single nucleotide polymorphism (SNP) has been constantly associated with diabetes mellitus (DM) and its vascular complications. The aim of this meta-analysis was to evaluate this association with combined evidences.
The systematic search was performed for studies published up to March 2021 which assess the associations between SERPINE1 rs1799889 SNP and the risks of DM, diabetic retinopathy (DR), diabetic cardiovascular disease (CVD) and diabetic nephropathy (DN). Only case-control studies were identified, and the linkage between SERPINE1 rs1799889 polymorphism and diabetic vascular risks were evaluated using genetic models.
51 comparisons were enrolled. The results revealed a significant association with diabetes risk in overall population (allelic: OR = 1.34, 95 % CI = 1.14-1.57, homozygous: OR = 1.66, 95 % CI = 1.23-2.14, heterozygous: OR = 1.35, 95 % CI = 1.08-1.69, dominant: OR = 1.49, 95 % CI = 1.18-1.88, recessive: OR = 1.30, 95 % CI = 1.06-1.59) as well as in Asian descents (allelic: OR = 1.45, 95 % CI = 1.16-1.82, homozygous: OR = 1.88, 95 % CI = 1.29-2.75, heterozygous: OR = 1.47, 95 % CI = 1.08-2.00, dominant: OR = 1.64, 95 % CI = 1.21-2.24, recessive: OR = 1.46, 95 % CI = 1.09-1.96). A significant association was observed with DR risk (homozygous: OR = 1.25, 95 % CI = 1.01-1.56, recessive: OR = 1.20, 95 % CI = 1.01-1.43) for overall population, as for the European subgroup (homozygous: OR = 1.32, 95 % CI = 1.02-1.72, recessive: OR = 1.38, 95 % CI = 1.11-1.71). A significant association were shown with DN risk for overall population (allelic: OR = 1.48, 95 % CI = 1.15-1.90, homozygous: OR = 1.92, 95 % CI = 1.26-2.95, dominant: OR = 1.41, 95 % CI = 1.01-1.97, recessive: OR = 1.78, 95 % CI = 1.27-2.51) and for Asian subgroup (allelic: OR = 1.70, 95 % CI = 1.17-2.47, homozygous: OR = 2.46, 95 % CI = 1.30-4.66, recessive: OR = 2.24, 95 % CI = 1.40-3.59) after ethnicity stratification. No obvious association was implied with overall diabetic CVD risk in any genetic models, or after ethnicity stratification.
SERPINE1 rs1799889 4G polymorphism may outstand for serving as a genetic synergistic factor in overall DM and DN populations, positively for individuals with Asian descent. The association of SERPINE1 rs1799889 SNP and DR or diabetic CVD risks was not revealed.
丝氨酸蛋白酶抑制剂-1(SERPINE1)rs1799889 单核苷酸多态性(SNP)一直与糖尿病(DM)及其血管并发症相关。本荟萃分析的目的是评估这一关联的综合证据。
系统检索了截至 2021 年 3 月评估 SERPINE1 rs1799889 多态性与糖尿病风险、糖尿病视网膜病变(DR)、糖尿病心血管疾病(CVD)和糖尿病肾病(DN)风险之间关联的研究。仅纳入病例对照研究,并使用遗传模型评估 SERPINE1 rs1799889 多态性与糖尿病血管风险的关联。
共纳入 51 项比较。结果显示,在总体人群中,SERPINE1 rs1799889 多态性与糖尿病风险显著相关(等位基因:OR=1.34,95%CI=1.14-1.57,纯合子:OR=1.66,95%CI=1.23-2.14,杂合子:OR=1.35,95%CI=1.08-1.69,显性:OR=1.49,95%CI=1.18-1.88,隐性:OR=1.30,95%CI=1.06-1.59),以及亚洲血统人群中(等位基因:OR=1.45,95%CI=1.16-1.82,纯合子:OR=1.88,95%CI=1.29-2.75,杂合子:OR=1.47,95%CI=1.08-2.00,显性:OR=1.64,95%CI=1.21-2.24,隐性:OR=1.46,95%CI=1.09-1.96)。在总体人群中,DR 风险与 SERPINE1 rs1799889 多态性显著相关(纯合子:OR=1.25,95%CI=1.01-1.56,隐性:OR=1.20,95%CI=1.01-1.43),在欧洲亚组人群中也有类似的结果(纯合子:OR=1.32,95%CI=1.02-1.72,隐性:OR=1.38,95%CI=1.11-1.71)。在总体人群中,SERPINE1 rs1799889 多态性与 DN 风险显著相关(等位基因:OR=1.48,95%CI=1.15-1.90,纯合子:OR=1.92,95%CI=1.26-2.95,显性:OR=1.41,95%CI=1.01-1.97,隐性:OR=1.78,95%CI=1.27-2.51),亚洲亚组人群中也有类似的结果(等位基因:OR=1.70,95%CI=1.17-2.47,纯合子:OR=2.46,95%CI=1.30-4.66,隐性:OR=2.24,95%CI=1.40-3.59),在进行种族分层后。在任何遗传模型中,或在进行种族分层后,SERPINE1 rs1799889 多态性与总体糖尿病 CVD 风险均无明显关联。
SERPINE1 rs1799889 4G 多态性可能是糖尿病和糖尿病肾病人群中一个重要的遗传协同因素,对亚洲血统的个体尤为显著。SERPINE1 rs1799889 SNP 与 DR 或糖尿病 CVD 风险之间的关联尚未揭示。