Genetic association study suggests a role for SP110 variants in lymph node tuberculosis but not pulmonary tuberculosis in north Indians
HUMAN IMMUNOLOGY
Authors: Abhimanyu; Jha, Pankaj; Jain, Ashima; Arora, Komal; Bose, Mridula
Abstract
Ethnic specificity is a key determinant in understanding the association of genetic variants with outcome of disease susceptibility. SP110, a component of the nuclear body, has been subjected to association studies with conflicting results. In this study we probed SP110 variants in pulmonary (PTB) and lymph node tuberculosis (LNTB) cases to explore their role in controlling susceptibility to Mycobacterium tuberculosis infection in north Indians. We genotyped 24 SP110 variants in over 140 north Indian tuberculosis cases and 78 ethnicity-matched controls. The SP110 gene variants were available from public databases. The cases and controls were free of any population stratification when subjected to Eigenstrat principal component analysis. Genotyping was carried out using the Sequenom MassARRAY platform. Applying exclusion criteria, 11 single nucleotide polymorphisms (SNPs) of the LNTB panel and 13 SNPs of the PTB panel passed all filters and were analyzed further. No significant association was observed between SP110 variants and FTB. Surprisingly, we discovered evidence of an association of SP110 variants with LNTB, a form of extrapulmonary tuberculosis, at 3 loci, namely, rs6436915, rs1427294, and rs1346311. When permutations analysis (n = 10,000) of allelic p values was undertaken, only rs1427294 passed the test with its p value remaining statistically significant. The C allele of rs1427294 exhibited a 5-fold risk of developing LNTB. No significant haplotypes were observed. In the pilot study presented here, our results provide evidence for the first time that SP110 may be a risk determinant locus in LNTB while confirming a doubtful role of SP110 in PTB in north Indians. In general, the results might indicate a role of SP110 variants in extrapulmonary tuberculosis rather than PTB. (C) 2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
Genetic immune and inflammatory markers associated with diabetes in solid organ transplant recipients
AMERICAN JOURNAL OF TRANSPLANTATION
Authors: Quteineh, Lina; Wojtowicz, Agnieszka; Bochud, Pierre-Yves; Crettol, Severine; Vandenberghe, Frederik; Venetz, Jean-Pierre; Manuel, Oriol; Golshayan, Dela; Lehmann, Roger; Mueller, Nicolas J.; Binet, Isabelle; van Delden, Christian; Steiger, Jurg; Mohacsi, Paul; Dufour, Jean-Francois; Soccal, Paola M.; Kutalik, Zoltan; Marques-Vidal, Pedro; Vollenweider, Peter; Recher, Mike; Hess, Christoph; Pascual, Manuel; Eap, Chin B.
Abstract
New-onset diabetes mellitus after transplantation (NODAT) is a complication following solid organ transplantation (SOT) and may be related to immune or inflammatory responses. We investigated whether single nucleotide polymorphisms (SNPs) within 158 immune- or inflammation-related genes contribute to NODAT in SOT recipients. The association between 263 SNPs and NODAT was investigated in a discovery sample of SOT recipients from the Swiss Transplant Cohort Study (STCS, n(1) = 696). Positive results were tested in a first STCS replication sample (n(2) = 489) and SNPs remaining significant after multiple test corrections were tested in a second SOT replication sample (n(3) = 156). Associations with diabetic traits were further tested in several large general population-based samples (n > 480 000). Only SP110 rs2114592C>T remained associated with NODAT in the STCS replication sample. Carriers of rs2114592-TT had 9.9 times (95% confidence interval [CI]: 3.22-30.5, P = .00006) higher risk for NODAT in the combined STCS samples (n = 1184). rs2114592C>T was further associated with NODAT in the second SOT sample (odds ratio: 4.8, 95% CI: 1.55-14.6, P = .006). On the other hand, SP110 rs2114592C>T was not associated with diabetic traits in population-based samples, suggesting a specific gene-environment interaction, possibly due to the use of specific medications (ie, immunosuppressants) in transplant patients and/or to the illness that may unmask the gene effect.