Abstract

Purpose: Background: In patients with sickle cell disease (SCD), pain results in varied physical and emotional consequences. Insufficient information about underlying mechanisms affecting pain remains a barrier to addressing SCD pain. Multiple biological and psychological factors (i.e., environmental stress) known to contribute to other pain conditions are understudied in SCD where the median survival (38 years for men and 42 years for women) is lower than the general population. Emotional stress has been shown to be a trigger of pain in patients with SCD. Genetics plays an important but still not fully-understood role in the variation of pain. The rs10877969 SNP in the Arginine vasopressin receptor 1A gene (AVPR1A) is associated with aspects of acute pain and stress-related to pain, but it is unknown whether the genotype frequency differs between those younger or older than the median survival age for SCD. Our aim was to determine the association between AVPR1A genotype with stress and age in adults with SCD who had chronic pain. Materials and methods: Materials and methods: In a cross-sectional study, 169 participants with SCD and chronic pain (100% African descent; 62% female, mean age 36.4±11.6 years [younger adults n =110, 18-39 years and older adults n=59, ≥40 years]), we used the Perceived Stress Questionnaire (PSQ). As a part of a larger study, we genotyped samples using the Axiom Precision Medicine Research Array. We used the Michigan Imputation server to examine our single nucleotide polymorphism (SNP) of interest, rs10877969. The SNP was evaluated as the imputed score was R2>0.8. We used ANOVA to compare stress by genotype and age (younger and older adults). Results: Results: The rs10877969 genotype frequency for the overall sample was: CC 47 (28%), CT 72 (43%), and TT 50 (30%). The genotype frequency was similar for older adults vs. younger adults: CC 16 (27%) vs. 31 (28%), CT 24 (41%) vs. 48 (44%), and TT 19 (32%) vs. 31 (28%). Mean stress scores were not significantly different by genotype: CC mean = 0.39 ± 0.16, CT mean = 0.41 ± 0.19, and TT mean = 0.36 ± 0.16, p=0.22. Mean stress scores also were not significantly different by genotype for younger adults: CC mean = 0.39 ± 0.15, CT mean = 0.44 ± 0.19, and TT mean = 0.36 ± 0.14, p=0.09 or older adults: CC mean = 0.37 ± 0.19, CT mean = 0.34 ± 0.16, TT mean = 0.34 ± 0.19, p=0.90. Mean stress scores were significantly lower (p<0.05) for the older adults (mean = 0.35 ± 0.18) than the younger adults (mean = 0.41 ± 0.17). Conclusion: Discussion-Conclusion: Younger adults had higher average stress than older adults. In contrast to prior research, in this study there was not an association between genotype and stress. Previously, the stand-out result was that individuals with SCD and CC genotype cited stress much less than the other two genotypes. The current result has a very different pattern. Further research is needed to examine stress and the rs10877969 genotype using other indicators of stress in this population. The authors do not declare any conflict of interest

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