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AB0083 Single nucleotide polymorphisms in lep – 2548 g>a and lepr + 668 a>g in rheumatoid arthritis mexican mestizos are associated with age at diagnosis, disease activity and anti-ccp antibodies
  1. E Gomez-Bañuelos1,
  2. E Chavarria-Avila1,
  3. K Arrona-Rios2,
  4. L González-Rosas3,
  5. J Aguilar-Arreola3,
  6. S Duran-Barragan1,
  7. H Avila-Armengol3,
  8. F Corona-Meraz1,
  9. A Saldaña-Millan1,
  10. R-E Navarro-Hernandez1,
  11. M Vázquez-Del Mercado1,3
  1. 1Instituto de Invesgitaciόn en Reumatología y del Sistema Musculoesquelético, Universidad de Guadalajara
  2. 2Servicio de Reumatologia, Division de medicina interna, Posgrado PNPC 004086, CONACYT
  3. 3Servicio de Reumatologia, Division de medicina interna, Posgrado PNPC 004086, CONACYT, Hospital Civil de Guadalajara, “Juan I. Menchaca”, Guadalajara, Mexico

Abstract

Background The role of adipose tissue in RA pathogenesis has been acknowledged since the high frequency of dyslipidemia and insulin resistance in these patients. Leptin, a pleiotropic adipokine, has been associated with inflammation markers and articular damage in RA and the anti-citrullinated protein antibodies. Notwithstanding, these findings have not been constant across different populations. These points towards that single nucleotide polymorphism (SNP) in leptin and its receptor might influence the participation of this adipokine in RA pathogenesis.

Objectives To determine the association of the SNPs LEP -2548 G>A and LEPR 668 A>G with adiposity, metabolic and inflammation markers in RA patients.

Methods We enrolled 116 patients with RA (ACR 1987) matched with 133 control subjects by age, gender, and body mass index (BMI). Subjects were evaluated for fat mass and skinfold thickness. Also, serum glucose, insulin, lipid profile, serum leptin (sLep), soluble leptin receptor, TNFa. In patients with RA we evaluated disease activity and anti-CCP. Genotypes of LEP -2548 G>A and LEPR 668 A>G were determined by PCR-RFPL using HhaI and MspI restriction enzymes.

Results There was no difference in genotypes distribution of LEP -2548 G>A and LEPR 668 A>G between RA and control. LEPR 668 G allele was associated with higher anti-CCP titers and disease activity score compared to LEPR 668A/A homozygotes, 4.2±1.7 vs. 3.46±1.2 P=0.012. LEP -2548A allele was associated with younger age of RA diagnosis vs. G/G homozygotes, 35.9±11.5 vs. 41.8±13.9 years old (P =0.045). OR for diagnosis before 40 years old was 2.7 (CI95% 1.04 – 7.45).

Conclusions LEP -2548 G>A is related with a younger age at diagnosis of RA and LEPR 668 G/G was associated with increased anti-CCP titers and disease activity. This suggests that there is an additive effect between chronic inflammation of RA and obesity were leptin may favor humoral immune response against citrullinated proteins and influence the severity of RA.

In preobese and obese patients with RA anti-CCP (+) there is an increased sLep production. LEP -2548 G>A is related with a younger age at diagnosis of RA and LEPR 668 G/G was associated with increased anti-CCP titers and disease activity. These suggests that there is an additive effect between chronic inflammation of RA and obesity were leptin may favors humoral immune response against citrullinated proteins and influence the severity of RA.

Disclosure of Interest None declared

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