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Endogenous Histamine and Cortisol Levels in Subjects with Different Histamine N-Methyltransferase C314T Genotypes

A Pilot Study

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Abstract

Background: Histamine N-methyltransferase (HNMT) catalyzes the methylation of histamine and plays an important role in histamine biotransformation in bronchial epithelium. Enzymatic activity of HNMT has been shown to be regulated by genetic factors, including polymorphisms in the HNMT gene. In this pilot study we determined endogenous levels of histamine and cortisol in plasma and whole blood samples from subjects with different genotypes for the HNMT C314T polymorphism, and investigated whether these parameters differed between individuals with the HNMT CC genotype and those with the CT genotype.

Methods: Blood samples were collected from 48 unrelated volunteers (36 males, 12 females), aged 21–40 years, who participated in the study. PCR-restriction fragment length polymorphism analysis was used to determine HNMT C314T genotypes. Erythrocyte HNMT activity was determined as well as plasma and whole blood levels of histamine and cortisol. Two-group comparisons of the various parameters were analyzed by Blocked Wilcoxon test and Wilcoxon Rank Sum test as appropriate.

Results: Thirty-seven subjects (24 Caucasians, three African Americans, one Middle Eastern, five Indians, three Chinese, and one Filipino) were found to have the homozygous CC genotype. Ten subjects (eight Caucasians, one Middle Eastern, and one Chinese) were heterozygous and one individual (Pakistani) was homozygous for the variant 314T allele. The frequency of HNMT CI heterozygotes in the small Caucasian cohort was 0.125. Median enzyme activity was significantly lower in subjects with the heterozygous CT genotype than in those with the homozygous CC genotype (485 vs 631 U/mL of red blood cells; p = 0.023). A broad range of histamine levels in plasma and whole blood was observed for all subjects. Whereas the median plasma histamine level was found to be higher in heterozygotes for the wild-type 314C allele than homozygotes (3.32 vs 2.30 nmol/L; p = 0.021), there was no difference between the two groups in histamine levels in whole blood. Cortisol levels were similar between individuals with the homozygous CC genotype and those with the heterozygous CT genotype.

Conclusion: Wide variability of plasma and whole-blood histamine levels was observed in subjects with different HNMT C314T genotypes. Endogenous levels of histamine are likely to be affected by various genes and polymorphisms.

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Acknowledgments

The authors thank Dr Richard Weinshilboum for providing the primers and Ms Bridget Bexho for coordinating the study. Statistical support from Dr Bob Wesley is greatly appreciated.

This work was supported in part by the American Foundation for Pharmaceutical Education (ACPE) and The Burroughs Wellcome Fund through the American Association of Colleges of Pharmacy New Investigators Program for Pharmacy Faculty (AACP-NIP) Award, and in part by the grant number 24211 from the National Institute of General Medical Sciences, National Institutes of Health. The authors have no conflict of interest.

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Authors and Affiliations

  1. Department of Clinical and Administrative Sciences, Mercer University Southern School of Pharmacy, Atlanta, Georgia, USA

    Yuen Yi Hon, Vicky E. Spratlin & Michael W. Jann

  2. Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, New York, USA

    William J. Jusko

  3. Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, People’s Republic of China

    Hong-Hao Zhou, Guo-Lin Chen, Dong Guo & Gan Zhou

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  1. Yuen Yi Hon
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Correspondence to Yuen Yi Hon.

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Hon, Y.Y., Jusko, W.J., Zhou, HH. et al. Endogenous Histamine and Cortisol Levels in Subjects with Different Histamine N-Methyltransferase C314T Genotypes. Mol Diag Ther 10, 109–114 (2006). https://doi.org/10.1007/BF03256450

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