Julie Stark1, Jamie Renbarger2, James Slaven3, Zhangsheng Yu3, Jenny Then2, Jodi Skiles2, Stephanie Davis4. 1. Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana. 2. Department of Hematology/Oncology, Indiana University School of Medicine, Indianapolis, Indiana. 3. Department of Biostatics, Indiana University School of Medicine, Indianapolis, Indiana. 4. Department of Pediatrics, Section of Pediatric Pulmonology, Allergyand Sleep Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
Abstract
RATIONALE: Pulmonary complications after hematopoietic stem cell transplant (SCT) are associated with increased mortality. Genetic markers for those at risk for pulmonary impairment post-SCT have not been widely investigated. METHODS: Forty-nine patients were retrospectively selected from a single institution's biorepository with linked clinical data. All subjects performed pre-SCT PFTs. Genotyping was conducted using the Infinium Exome-24 BeadChip. Four single nucleotide polymorphisms (SNPs) were selected (rs1800871, rs1695, rs1800629, rs12477314) and evaluated for association with PFT parameters as change over time from baseline. Associations between SNPs and PFT parameters were assessed and adjusted for the following confounding variables: age, gender, and race. RESULTS: Using the recessive genetic model, patients with one or two minor alleles for the glutathione S-transferase P1 (GSTP1) SNP rs1695 had a lower decline in FEV1 and FEF25-75 at 1-year post-SCT compared to patients who were homozygous for the ancestral allele (adjusted P-values <0.01 and 0.02, respectively). No other SNPs were significantly associated with other PFT parameters. CONCLUSIONS: Our findings suggest that GSTP1 genotype may be associated with lung function during the first year post-SCT. Identifying and investigating genes that predispose patients to pulmonary complications after SCT may allow for more personalized patient management based on pre-emptive genetic testing. The glutathione S-transferase gene merits further investigation.
RATIONALE: Pulmonary complications after hematopoietic stem cell transplant (SCT) are associated with increased mortality. Genetic markers for those at risk for pulmonary impairment post-SCT have not been widely investigated. METHODS: Forty-nine patients were retrospectively selected from a single institution's biorepository with linked clinical data. All subjects performed pre-SCT PFTs. Genotyping was conducted using the Infinium Exome-24 BeadChip. Four single nucleotide polymorphisms (SNPs) were selected (rs1800871, rs1695, rs1800629, rs12477314) and evaluated for association with PFT parameters as change over time from baseline. Associations between SNPs and PFT parameters were assessed and adjusted for the following confounding variables: age, gender, and race. RESULTS: Using the recessive genetic model, patients with one or two minor alleles for the glutathione S-transferase P1 (GSTP1) SNP rs1695 had a lower decline in FEV1 and FEF25-75 at 1-year post-SCT compared to patients who were homozygous for the ancestral allele (adjusted P-values <0.01 and 0.02, respectively). No other SNPs were significantly associated with other PFT parameters. CONCLUSIONS: Our findings suggest that GSTP1 genotype may be associated with lung function during the first year post-SCT. Identifying and investigating genes that predispose patients to pulmonary complications after SCT may allow for more personalized patient management based on pre-emptive genetic testing. The glutathione S-transferase gene merits further investigation.
Authors: Young-Jee Kim; Graham L Hall; Kathy Christoph; Rebeka Tabbey; Zhangsheng Yu; Robert S Tepper; Howard Eigen Journal: Pediatr Pulmonol Date: 2011-11-11
Authors: Angela Panoskaltsis-Mortari; Matthias Griese; David K Madtes; John A Belperio; Imad Y Haddad; Rodney J Folz; Kenneth R Cooke Journal: Am J Respir Crit Care Med Date: 2011-05-01 Impact factor: 21.405
Authors: Francisco Rodriguez; Cristian de la Roza; Rosendo Jardi; Melanie Schaper; Rafael Vidal; Marc Miravitlles Journal: Chest Date: 2005-05 Impact factor: 9.410
Authors: Jill P Ginsberg; Richard Aplenc; Joseph McDonough; James Bethel; John Doyle; Daniel J Weiner Journal: Pediatr Blood Cancer Date: 2010-03 Impact factor: 3.167