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Associations Between Genetic Variants in Vitamin D Metabolism and Asthma Characteristics in Young African Americans
  1. Dinesh K. Pillai, MD*†‡,
  2. Sabah F. Iqbal, MD†‡§,
  3. Angela S. Benton, BAS,
  4. Jennifer Lerner, BS,
  5. Andrew Wiles, BS,
  6. Matthew Foerster, BS,
  7. Tugba Ozedirne, MD, JD, MPP,
  8. Henry P. Holbrook, MD, JD, MPP,
  9. Perry W. Payne Jr, MD, JD, MPP†¶**,
  10. Heather Gordish-Dressman, PhD,
  11. Stephen J. Teach, MD, MPH‡§††,
  12. Robert J. Freishtat, MD, MPH†‡§
  1. From the *Division of Pulmonary Medicine, Children's National Medical Center; †Department of Integrative Systems Biology, George Washington University School of Medicine and Health Sciences; ‡Department of Pediatrics, George Washington University School of Medicine and Health Sciences; §Division of Emergency Medicine, Children's National Medical Center, Washington, DC; ∥University of California at Davis, Davis, CA; ¶Department of Clinical Research and Leadership, George Washington University School of Medicine and Health Sciences; **Department of Health Policy, George Washington School of Public Health and Health Services; and ††Center for Clinical and Community Research, Children's National Medical Center, Washington, DC.
  1. Received November 16, 2010, and in revised form April 11, 2011.
  2. Accepted for publication April 20, 2011.
  3. Reprints: Sabah F. Iqbal, MD, 111 Michigan Ave, NW, Washington, DC 20010. E-mail: siqbal{at}cnmcresearch.org.
  4. The first and second authors (D.K.P. and S.F.I.) contributed equally to this paper.
  5. Grant Support: This study was supported by Grant M01RR020359 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH.
  6. Additional support came from the following grants: K23RR020069 (R.J.F.), P20MD000198 (R.J.F.), M01RR020359 (R.J.F.), K12HL090020 (D.K.P., S.F.I., and P.W.P.) from the National Institutes of Health, Bethesda, MD; the Sheldon C. Siegel Investigator Award Grant from the Asthma and Allergy Foundation of America (R.J.F.); and institutional grants from Children's National Medical Center, Washington, DC (R.J.F.).

A Pilot Study

Abstract

Introduction Low vitamin D levels have been associated with asthma severity in children. Young, urban African Americans (AAs) have high rates of hypovitaminosis D and asthma. Our objective was to determine associations between variants in vitamin D metabolism genes and asthma characteristics in a pilot study of young urban AAs.

Materials and Methods Two urban AA cohorts of subjects aged 6 to 20 years (139 subjects with asthma and 74 subjects without asthma) were genotyped for 12 single nucleotide polymorphisms (SNPs) in 3 vitamin D metabolism genes: VDR (vitamin D receptor), CYP24A1 (cytochrome P450 vitamin D 24-hydroxylase), and CYP2R1 (cytochrome P450 vitamin D 25-hydroxylase). In a case-control analysis, SNPs were studied for associations with an asthma diagnosis. Within the asthmatic cohort, SNPs were analyzed for associations with quantitative asthma characteristics. All analyses were adjusted for age, sex, and body mass index percentile.

Results Only the CYP2R1 SNP rs10766197 homozygous minor genotype was associated with asthma (P = 0.044). CYP24A1 SNP rs2248137 was associated with lower vitamin D levels (P = 0.006). Within the asthma cohort, multiple significant associations between SNPs and asthma characteristics were identified; VDR SNP rs2228570 was associated with the higher nighttime asthma morbidity scores (P = 0.04), lower baseline spirometric measures (P < 0.05), 1 or more positive aeroallergen skin test (P = 0.003), and increased immunoglobulin E levels (P < 0.001).

Discussion This pilot study demonstrates that variants in vitamin D metabolism genes are associated with quantitative asthma characteristics in young, urban AAs. The collection of these associations provides evidence for the need for a large population-based study of vitamin D-relevant SNPs in this cohort.

Key Words
  • asthma
  • vitamin D
  • African American youth
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