Cytokines genes and autosomal dominant polycystic kidney disease in a brazilian population

Prévia do material em texto

P108 KIR-HLA LIGAND GENOTYPIC INTERACTION AND SUSCEPTIBILITY TO INFLAMMATORY
BOWEL DISEASE. Elizabeth A. Trachtenberg 1, Julia B.M. Udell 1, Kazutoyo
Osoegawa 1, Martha B. Ladner 1, David A. Noonan 1, Dermot P.B. McGovern 2,
Jerome I. Rotter 3, Kent D. Taylor 3, Henry A. Erlich 4. 1 Stanford University, Palo Alto,
CA, United States; 2 Cedars-Sinai Medical Center, Los Angeles, CA, United States; 3 Los
Angeles Biomedical Research Institute, Harbor-UCLA, Torrance, CA, United States;
4 Children’s Hospital Oakland Research Institute, Oakland, CA, United States.
Aim: To elucidate the contribution of the Killer Ig-like Receptors (KIR) and their Human Leukocyte Antigen
(HLA) ligands to Crohn’s Disease (CD) and Ulcerative Colitis (UC), the clinical subtypes of inflammatory bowel
disease (IBD), an immune-mediated disease of the digestive tract.
Methods and Cohorts: MALDI-TOF mass spectrometry was used to profile the presence/absence of 16 KIR
loci. HLA loci were genotyped using reverse format SSO strip, Luminex rSSO and a Roche 454 NGS system
developed in our laboratory for complete HLA class I and II genotyping. Protein sequence data corresponding
to HLA allelic typing was used to determine KIR ligands: Bw4/6 and C1/C2 epitope groups were assigned using
residues at positions 77–83 in HLA-B and -C. Case-control analysis of 1232 Caucasian IBD patients (461 with
UC: 277 medically refractory (MR), 184 non-MR; 771 with CD) and 203 Caucasian controls was performed
using the chi-square test to compare the distribution of KIR genes KIR2DL2, KIR2DL3 and KIR3DL1, KIR3DS1
and their respective HLA ligands,C1, C2 and Bw4, across various disease phenotypes, including CD, UC and
MR-UC disease.
Results: The homozygous genotypic combination of KIR2DL3, KIR3DL1 (homozygous KIR A/A haplotype)
and Bw6 (absence of Bw4) with both C1 and C2 ligands present was shown to be highly significantly protec-
tive against ulcerative colitis (OR = 0.29, p < 0.001). No significant association was found with KIR loci and
their HLA-ligands with CD, or with non-MR versus MR-UC.
Conclusions: These data reveal a central role for a specific combination of KIRs and HLA ligands (i.e., homo-
zygous KIR A haplotype, absence of Bw4 and C1/C2 heterozygosity) in protecting against UC disease and
underscore the importance of analyzing genotypes of KIR together with their HLA ligands in disease associ-
ation studies.
P109 CYTOKINES GENES AND AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE IN A
BRAZILIAN POPULATION. Everton F. Alves, Sueli Donizete Borelli, Luiza T. Tsuneto.
State University of Maringá, Maringá, Brazil.
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is caused mainly by mutations in genes PKD1 or
PKD2, which result in accumulation of cysts in the kidneys. In this study we investigated the existence of pos-
sible associations between variants in cytokine genes and cytokine receptors genes: IL1A-889 (rs1800587),
IL1B-511, +3962 (rs16944, rs1143634), IL1R1970 (rs2234650), IL1RA11100 (rs315952), IL4RA +1902
(rs1801275), IL12–1188 (rs3212227), IFNG +874 (rs2430561), TGFB1 codon 10,codon 25 (rs1982073,
rs1800471), TNF-308, �238 (rs1800629, rs361525), IL2 �330 +166 (rs2069762, rs2069763), IL4–1098,
�590, �33 (rs2243248, rs2243250, rs2070874), IL6–174, nt565 (rs1800795, rs1800797) e IL10–1082,
�819, �592(rs1800896, rs1800871, rs1800872) and ADPKD. The samples were constituted by 60 patients
with clinical and laboratorial diagnostic of ADPKD and 113 individuals without the disease historical, they
were not related. Genotyping of the variants in genes for cytokines and cytokine receptors were performed
by the PCR-SSP method (cytokine genotyping Kit, Invitrogen™). Association studies were calculated by Fish-
er’s exact test between frequencies by haplotypes, genotypes and alleles. Some differences were observed in
proinflammatory cytokines: TNF-308, �238 ( GG/ GG [OR = 0.44]), �238 (G/G [OR = 0,35],G/A [OR = 2.84], G
[OR = 0.38] and A [OR = 2.62]) and IL2 �330, +166 (GG/GG [OR = 4.93]), �330 (G/G [OR = 2.56]), and anti -
inflammatory TGFB1códon 10 (C/C [OR = 2.22] and C [OR = 1.66]) and IL4 �1098, �590 �33 ( TCC/GCC
[OR = 2.14]), �1098 (T/G [OR = 2.31]). We suggested that cytokine gene SNPs may influence in the predispo-
sition to ADPKD.
126 Abstracts / Human Immunology 75 (2014) 50–141