Genotype Ser⁴¹³/Ser of PAI‐2 polymorphism Ser⁴¹³/Cys is associated with anti‐phospholipid syndrome and systemic lupus erythematosus in a familial case: comparison with healthy controls

Abstract

Background: We describe a family with a 7‐year‐old proband case diagnosed with systemic lupus erythematosus (SLE) plus secondary anti‐phospholipid syndrome (APS) as well as two affected paternal aunts. We compared the frequency of these polymorphisms with healthy controls.

Objectives: To evaluate the mode of inheritance in this familial case of APS and SLE and the possible association of plasminogen activator inhibitor‐1 (PAI‐1) −675 4G/5G and PAI‐2 Ser⁴¹³/Cys polymorphisms. To compare the genotype frequency of these polymorphisms with the results found in a Mexican Mestizo population.

Methods:PAI‐1 −675 4G/5G and PAI‐2 Ser⁴¹³/Cys were determined by the polymerase chain reaction restriction fragment length polymorphism (PCR‐RFLP) technique using Bsl I and Mwo I on four generations of the family studied. PAI‐2 Ser⁴¹³/Cys polymorphism was also determined in 50 healthy individuals of Mexican Mestizo origin.

Results: The family pedigree demonstrated that this family did not follow a Mendelian inheritance pattern. When the PAI‐2 Ser⁴¹³/Cys polymorphism was examined, we found that 60% (3/5) of the relatives homozygous to Ser⁴¹³/Ser were affected with SLE and/or APS (p = 0.027). The proband case was 4G/5G genotype for the PAI‐1 −675 4G/5G polymorphism. No differences between healthy controls of the Mexican Mestizo population and the family studied for the PAI‐2 Ser⁴¹³/Cys polymorphism or PAI‐1 −675 4G/5G polymorphisms were found.

Conclusions: Our data indicate that this family did not follow the Mendelian inheritance pattern. The Ser⁴¹³/Ser genotype demonstrated in 60% of the affected members (3/5) of this family might increase the risk for autoimmune syndromes such as APS or SLE.