PADI4 polymorphisms and the functional haplotype are associated with increased rheumatoid arthritis susceptibility: A replication study in a Southern Mexican population.

Rheumatoid arthritis (RA) is a common autoimmune disease with a complex genetic background. The peptidyl arginine deiminase type IV (PADI4) gene has been associated with RA susceptibility in several populations. We addressed the relationship between three exonic PADI4 gene single nucleotide polymorphisms (SNPs) PADI4_89 (rs11203366), PADI4_90 (rs11203367) and PADI4_92 (rs874881) and related haplotypes with RA in a population from Southern México. This study included 200 RA patients and 200 control subjects. The SNPs were evaluated using the polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) technique, and antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA). In this population, the minor alleles of PADI4_89∗G, PADI4_90∗T and PADI4_92∗G gene polymorphisms were associated with RA susceptibility (OR=1.34, p=0.04; OR=1.35, p=0.03; OR=1.34, p=0.04; respectively). The GTG haplotype was also significantly associated with RA (OR=2.27 95%CI=1.18-4.41; p=0.008), but did not show association with levels of anti-CCP antibodies and clinical parameters. In conclusion, our replication study in a Southern Mexican population suggests that PADI4 individual polymorphisms and the related susceptibility haplotype (GTG) are also genetic risk markers for RA.

Distribution of --844 G/A and Hind III C/G PAI-1 polymorphisms and plasma PAI-1 levels in Mexican subjects: comparison of frequencies between populations.

Several polymorphisms have been described in the PAI-1 gene including the -844 G/A and Hind III C/G polymorphisms. These polymorphisms have been associated with different diseases such as preeclampsia and cardiovascular diseases. The allele and genotype frequencies of both PAI-1 polymorphism where investigated in Mexican subjects and compared with other healthy worldwide populations. The hematological and biochemical parameters where classified according each genotype in our studied group. One hundred Mexican subjects were recruited. Demographic data and hematological and biochemical parameters were collected, and genomic DNA isolation was performed in all the participants. Screening of both polymorphisms studied was made by polymerase chain reaction and restriction analysis. Levels of plasminogen activator inhibitor-1 in plasma were measured by ELIS-ARA plasminogen activator inhibitor antigen kit. The -844 and Hind III genotypes frequencies were as follows: 49% (G/G), 40% (G/A), 11% (A/A) and 50% (C/C), 44% (C/G), 6% (G/G), respectively. The wild-type genotypes (G/G and C/C) were significantly higher with respect to the compared populations. In addition, a significant increase of apolipoprotein A1 in the carriers of G/A -844 and C/G Hind III genotypes was observed. However, when the plasma plasminogen activator inhibitor levels were analyzed with respect to each genotype and haplotype, no significant differences were found.