Plasminogen activator inhibitor-1 polymorphisms (−844 G>A and HindIII C>G) in systemic lupus erythematosus: association with clinical variables

Abstract

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the presence of autoantibodies against nuclear autoantigens as well as cytoplasmic and circulating proteins. Recent studies have demonstrated mechanisms responsible for modulation of the immune response by the plasminogen activator inhibitor-1 (PAI-1). Furthermore, the endogenous PAI-1 has shown to promote a Th2 immune response. We assessed the -844 G>A and HindIII C>G PAI-1 polymorphisms in SLE. In a case-control study of 71 SLE patients classified according to ACR criteria and 71 healthy subjects (HS). The A allele of -844 PAI-1 polymorphism showed a significant difference in SLE patients (41%) when compared with HS (27%) [P = 0.01; OR = 1.8, 95%, CI = 1.1-3.0]. In addition, the -844 G>A PAI-1 polymorphism was associated with increased risk for SLE in a dominant genetic model (G/G vs. G/A + A/A; OR = 2.3, 95% CI = 1.14-4.44). Also, anti-RNP positive antibodies in SLE were associated with G/G -844 PAI-1 genotype. The HindIII polymorphism did not show any differences. The haplotype analysis showed that the AC haplotype confers susceptibility to SLE (OR = 3.1, 95% CI, 1.45-6.52; P = 0.003). The AC haplotype of the -844 and HindIII PAI-1 polymorphism might be an additional susceptibility factor to SLE in Mexicans.

Relationship of metabolic syndrome and its components with -844 G/A and HindIII C/G PAI-1 gene polymorphisms in Mexican children

“…Regarding the distribution of genotype and allele frequencies of both polymorphisms, for the HindIII C/G polymorphism we found a high frequency of C allele, similar to previous reports in Mexican mestizo population and Caucasian population, however the G allele frequency was lower in Mexican population [18,21,29]. On the other hand, the -844 G/A polymorphism we observed that is distributed inversely to those reported in Caucasian populations, in which the A allele is more frequent than the G allele [12,18,19].…”

“…Association studies have shown that polymorphisms located in the promoter region of PAI-1 gene shows a relationship with the concentrations of lipids (low HDL) in Mexico-American population [16,17]. One of the polymorphisms in the promoter PAI-1 gene is the -844 G/A polymorphism, which has been associated with risk factors such as increased plasma levels of PAI-1, glucose, insulin resistance, triglycerides and low HDL, as well as with several diseases including deep vein thrombosis, coronary artery disease, rheumatoid arthritis and systemic lupus erithematosus [18-21]. Other SNP that is interesting is the HindIII C/G polymorphism located in the 3' untranslated region (UTR) of PAI-1 gene, which has been related to high levels of cholesterol and insulin in myocardial infarction patients [22].…”

The -844 G>A PAI-1 Polymorphism Is Associated with Acute Coronary Syndrome in Mexican Population

“…As it was established previously, we found differences in the genetic distribution in the HS group compared with other populations, including Europeans, Asians, and Sub-Sahara Africans, but not with the African American group and a previous report of Western Mexicans [ 16 ]. The own genetic structure of the Mexican Mestizo population, composed mainly with Spanish (53.2%) and American native (30.8%) genes, can explain these differences [ 23 ].…”

“…We compared the HS frequencies with other populations. The A allele prevalence was 23% in Sub-Saharan African, 27% in Mexican, 28% in Afro-American, 41% in Hispanic, 49% in Asian, and 56% in European populations [ 16 , 18 ]. The genetic distribution of the -844 G>A polymorphism in this cohort was different to those reported in Sub-Saharan African, Asian, and Europeans populations ( P < 0.01).…”

“…The sample size was calculated based on the minor allele frequency of the -844 G>A PAI-1 polymorphism reported in Mexican Mestizo population by Padilla-Gutiérrez et al [ 16 ] and we obtained at least 148 alleles using the Kelsey formula [ 17 ]. It means that, in order to detect differences, at least 74 individuals per group are needed with 95% confidence interval and statistical power of 80%.…”