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AB0371 Lepr 668 A>g Snp is Associated with Titers of Anti-CCP Antibodies and Erythrocyte Sedimentation Rate in Mexican Mestizo Patients with Rheumatoid Arthritis
  1. E. Gomez1,
  2. M. Vazquez-Del Mercado1,
  3. R.E. Navarro-Hernandez1,
  4. F. Corona-Meraz1,
  5. P. Madrigal-Ruiz1,
  6. E. Chavarria-Avila1,
  7. J. Aguilar-Arreola2,
  8. J. Perez-Cruz2
  1. 1Rheumatology, Instituto de Investigacion en Reumatologia y del Sistema Musculoesquelético
  2. 2Rheumatology, Hospital Civil “Juan I. Menchaca”, Guadalajara, Mexico

Abstract

Background Dyslipidemia and insulin resistance (IR) are common metabolic disorders present in rheumatoid arthritis (RA). Inflammatory cytokines in RA may cause redistribution and dysfunction of adipose tissue favoring development of these metabolic alterations. The adipokine leptin participates in energy expenditure, food ingestion, insulin sensitivity, proliferation and differentiation of immune cells. In RA leptin induce production of proinflammatory citokines and the differentiation of effector lymphocytes. Also, and adequate and regulated signaling through leptin is essential for adipose tissue functioning. The single nucleotide polymorphism 668 A>G in leptin receptor (LepR) gene LEPR causes the aminoacid change Gln223Arg in the extracellular portion of LepR. These polymorphism has been associated with serum leptin receptor (sLepR) and obesity among different populations.

Objectives To study the association between LEPR Gln223Arg genotypes in Mexican mestizos with rheumatoid arthritis, adiposity, insulin resistance and disease activity.

Methods We included 73 patients with RA and 96 control subjects matched by body mass index (BMI) according to WHO classification (Normal weight 20-25 kg/m2, Pre-Obese 25-30 kg/m2 and Obese >30 kg/m2). sLepR, TNFa, anti-CCP antibodies and insulin were determined by ELISA. Body composition was analyzed by electric bioimpedance. C-reactive protein, serum lipids and glucose were measured by standard methods. Genotypes of LEPR 668 A>G were determined by PCR-RFLP using restriction enzyme MspI. Statistics were analized with PASW Statistics v18.0 software.

Results Patients with RA and obesity had higher visceral fat accumulation and less accumulation of subcutaneous adipose tissue in comparison with controls. RA patients had higher serum insulin and HOMA-IR than controls in every BMI category. sLepR had a negative correlation with total fat mass (r = -0.445, P<0.001) and erythrocyte sedimentation rate. Genotypes frequencies were according to Hardy-Weinberg's principle. Frequency of genotypes A/A, A/G y G/G in RA was 0.35, 0.53 and 0.11, respectively, without difference in genotype frequencies and controls, P=0.67. There was no association with LEPR 668 A>G genotypes and adiposity or HOMA-IR in patients with RA. G/G (Arg/Arg) genotype and G (Arg) allele carriers had higher serum erythrocyte sedimentation rate and higher serum anti-CCP antibodies in patients with RA.

Conclusions RA patients have a fat mass distribution that favors insulin resistance. Lower sLepR is associated with adiposity in patients with RA. Arg/Arg genotype of LEPR 668 A>G is associated with higher erythrocyte sedimentation rate and higher serum anti-CCP antibodies in RA. LEPR A>G was not associated with adiposity or metabolic markers in RA.

Disclosure of Interest None declared

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