@article{f6c52619ac904044ab683052189f2aab,
title = "Genetic variants of GCH1 associate with chronic and acute crisis pain in African Americans with sickle cell disease",
abstract = "The multidimensional nature of pain in sickle cell disease (SCD) has rendered its therapeutic management extremely challenging. In this study, we explored the role of five single nucleotide polymorphisms (SNPs) of candidate gene GCH1 in SCD pain. Composite pain index (CPI) scores and acute care utilization rates were used as phenotype markers. Rs8007267 was associated with chronic pain (additive model: B = –3.76, p = 0.037; dominant model: B = –5.61, p = 0.021) and rs3783641 (additive model: incident rate ratio [IRR] = 1.37, p = 0.024; recessive model: IRR = 1.81, p = 0.018) with utilization rate. These associations persisted when subjects with HbSS and HbSβ° genotype only were analyzed. We also identified two haploblocks (rs10483639[G>C]-rs752688[C>T]-rs4411417[T>C] and rs3783641[T>A]-rs8007267[T>C]) with SNPs in high linkage disequilibrium. Of these, haplotype T-C of haploblock rs3783641-rs8007267 showed significant association with rate of utilization (odds ratio [OR] = 0.31, p = 0.001). Our study indicates potential contribution of GCH1 polymorphisms to the variability of pain in African Americans with SCD.",
author = "Nilanjana Sadhu and Jhun, {Ellie H.} and Yingwei Yao and Ying He and Molokie, {Robert E.} and Wilkie, {Diana J.} and Wang, {Zaijie Jim}",
note = "Funding Information: This work was supported in part by grants from the Illinois Department of Public Health (IDPH) and the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) (R01HL124945, R01HL098141, and R35HL140031). EJ was supported by a predoctoral fellowship from the National Institute of Dental and Craniofacial Research (NIDCR) (T32DE018381). YH is supported by a Pathway to Independence Award (K99HL133590). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the IDPH, NIH, NHLBI, NIDCR, or the Veteran's Administration. Funding Information: This work was supported in part by grants from the Illinois Department of Public Health (IDPH) and the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) (R01HL124945, R01HL098141, and R35HL140031). EJ was supported by a predoctoral fellowship from the National Institute of Dental and Craniofacial Research (NIDCR) (T32DE018381). YH is supported by a Pathway to Independence Award (K99HL133590). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the IDPH, NIH, NHLBI, NIDCR, or the Veteran's Administration. Publisher Copyright: {\textcopyright} 2018",
year = "2018",
month = oct,
doi = "10.1016/j.exphem.2018.07.004",
language = "English",
volume = "66",
pages = "42--49",
journal = "Experimental Hematology",
issn = "0301-472X",
publisher = "Elsevier Inc.",
}