The -675 4G/5G PAI-1 polymorphism confers genetic susceptibility to systemic lupus erythematosus, its clinical manifestations, and comorbidities in Mexican-Mestizo population.
Systemic lupus erythematosus (SLE) involves a broad range of factors that contribute to the development of the disease and its comorbidities. Genetic predisposition influences the development of SLE, and the -675 4G/5G PAI-1 polymorphism has been associated with several pathologies with a chronic inflammatory component. Our objective was to investigate the genetic association between the -675 4G/5G PAI-1 polymorphism with SLE, its clinical manifestations, and comorbidities in a Mexican-Mestizo population. The -675 PAI-1 polymorphism was determined by PCR-RFLP in 716 subjects: 293 SLE patients and 423 control subjects. Significant associations for SLE genetic susceptibility were found in carriers of 4G/5G (OR = 2.63; CI 1.81-3.87; p < .001) and 4G/4G (OR = 2.70; CI 1.62-4.51; p < .001) genotype in comparison with the 5G/5G genotype; 4G allele carriers also presented genetic risk for SLE (OR = 1.63; CI 1.31-2.03; p < .001) compared to the 5G allele. Following a dominant genetic model, a similar association was found with the 4G allele to SLE (OR = 2.66; CI1.84-3.84; p < .001). The 4G/5G genotype was associated with shorter disease duration (p = .039), as well as lower levels of haemoglobin (p = .001) and haematocrit (p = .009); the need for prednisone treatment (p = .001), higher BMI (p = .03), presence of type 2 DM (p = .015), clinical activity (Mex-SLEDAI = 57%; p = .047), Chronicity (SLICC-ACR = 0; p = .015) and CRP levels (p = .015) were associated with 5G/5G genotypes. In conclusion, the -675 4G/5G and 4G/4G PAI-1genotypes were found as genetic risk markers of susceptibility for SLE in the Mexican-Mestizo population, and each genotype could influence the clinical manifestations and comorbidities differently in SLE.
['Anaya-Macias|B U|BU|', 'De la Cruz-Mosso|U|U|', 'Palafox-Sánchez|C A|CA|', 'Parra-Rojas|I|I|', 'Martínez-Bonilla|G|G|', 'González-López|L|L|', 'Gámez-Nava|J I|JI|', 'Pérez-Guerrero|E E|EE|', 'Barrientos-Avalos|S L|SL|', 'Muñoz-Valle|J F|JF|']
D000293:Adolescent D000328:Adult D000483:Alleles D054458:Amplified Fragment Length Polymorphism Analysis D002908:Chronic Disease D015897:Comorbidity D003430:Cross-Sectional Studies D003924:Diabetes Mellitus, Type 2 D050171:Dyslipidemias D005260:Female D005787:Gene Frequency D020022:Genetic Predisposition to Disease D006400:Hematocrit D006454:Hemoglobins D006579:Heterozygote D006801:Humans D008180:Lupus Erythematosus, Systemic D008297:Male D008800:Mexico D008875:Middle Aged D009765:Obesity D017395:Plasminogen Activator Inhibitor 1 D012150:Polymorphism, Restriction Fragment Length D011241:Prednisone D055815:Young Adult
polymorphism Systemic lupus erythematosus plasminogen activator inhibitor-1