title: The extrapituitary prolactin promoter polymorphism is associated with rheumatoid arthritis and anti-CCP antibodies in Mexican population.
abstract: Prolactin (PRL) is a hormone-cytokine that has been involved in autoimmunity due to its immunoregulatory and lymphoproliferative effects. It is produced by various extrapituitary sites including immune cells, under control of a superdistal promoter that contains a single nucleotide polymorphism -1149 G/T previously associated with rheumatoid arthritis (RA) susceptibility in European population. The aim of this study was to investigate the association of the extrapituitary PRL -1149 G/T promoter polymorphism with clinical parameters, clinical activity and disability indices in RA patients from Western Mexico and to analyze the PRL mRNA expression according to the PRL -1149 G/T promoter polymorphism in total leucocytes from RA patients and controls. We conducted a case-control study that included 258 RA patients and 333 control subjects (CS). The DNA samples were genotyped using the PCR-RFLP method and the PRL mRNA expression was determined by quantitative real time PCR. PRL serum levels and antibodies to cyclic citrullinated peptides (anti-CCP) were measured with ELISA. We found significant differences in the genotype (p=0.022) and allelic (p=0.046) distribution of the polymorphism between RA patients and control subjects. According to the dominant genetic model, there is an association between the T allele (GT+TT genotypes) and decreased RA susceptibility in comparison to the G allele carriers (GG genotype) (OR 0.64, 95% CI 0.45-0.92; p=0.011). The T allele carriers (GT+TT genotypes) had lower titers of anti-CCP antibodies in comparison to the G allele carriers (GG genotype) (median, 66 U/mL vs. 125 U/mL; p=0.03). Furthermore, the GG homozygotes had higher PRL mRNA expression in comparison to the GT heterozygotes, and this latter with respect to the TT homozygotes, in both groups (RA: 1>0.72>0.19; CS: 1>0.54>0.28). However, PRL serum levels were similar in both groups. Our results suggest that the PRL -1149 T allele is a genetic marker for decreased RA susceptibility and is associated with lower titers of anti-CCP antibodies in Mexican population. We also suggest influence of genotype upon PRL mRNA expression.
authors: Doctorado en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico. zyanya_reyes@hotmail.com
authors: Zyanya
authors: Z
authors: Reyes-Castillo
authors: Ana Laura
authors: AL
authors: Pereira-Suárez
authors: Claudia Azucena
authors: CA
authors: Palafox-Sanchez
authors: Héctor
authors: H
authors: Rangel-Villalobos
authors: Ciro
authors: C
authors: Estrada-Chávez
authors: Edith
authors: E
authors: Oregón-Romero
authors: Luis Ignacio
authors: LI
authors: Angel-Chávez
authors: Salvador
authors: S
authors: Muñoz-Barrios
authors: Miriam Ruth
authors: MR
authors: Bueno-Topete
authors: José Francisco
authors: JF
authors: Muñoz-Valle
mesh_terms: D000328:Adult; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D001323:Autoantibodies / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D017058:Mexican Americans / Q000235:genetics; D008800:Mexico; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D011110:Polymorphism, Genetic; D011388:Prolactin / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D001323:Autoantibodies; D010456:Peptides, Cyclic; D012333:RNA, Messenger; C487763:cyclic citrullinated peptide; D011388:Prolactin