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The role of single nucleotide variant rs3819817 of the Histidine Ammonia-Lyase gene and 25-Hydroxyvitamin D on bone mineral density, adiposity markers, and skin pigmentation, in Mexican population

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Abstract

Purpose

Vitamin D (VD) deficiency and osteoporosis have become a global public health problem. A variant in the Histidine Ammonia-Lyase (HAL) gene has been associated with VD levels and bone mineral density (BMD). However, whether this variant has an influence on VD levels and BMD in Mexican adults remain unclear.

Methods

This cross-sectional analysis included 1,905 adults participating in the Health Worker Cohort Study and 164 indigenous postmenopausal women from the Metabolic Analysis in an Indigenous Sample (MAIS) cohort. The rs3819817 variant was genotyped by TaqMan probe assay. Total 25 hydroxyvitamin D levels were measured by DiaSorin Liaison. BMD at the different sites was assessed through dual-energy X-ray absorptiometry. Linear and logistic regression models were performed to evaluate the associations of interest.

Results

The prevalence of VD deficiency was 41%, showing differences between sexes. Obesity and skin pigmentation were associated with lower levels of VD in males and females. rs3819817-T allele was associated with low levels of 25-hydroxyvitamin D, VD deficiency, and hip and femoral neck BMD values (g/cm2). We found two interactions with VD levels, one between adiposity and rs3819817-T allele (P = 0.017) and another between skin pigmentation and rs3819817-T allele (P = 0.019). In indigenous postmenopausal women, we observed higher VD levels in the southern region compared to the northern region (P < 0.001); however, we did not observe differences by genotype.

Conclusion

Our findings confirm that the genetic variant rs3819817 has an essential function in VD levels and BMD and suggests a role in skin pigmentation in the Mexican population.

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Availability of data

The data that support the findings of this study are available from the corresponding author, RV-C, upon reasonable request.

Code availability

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Acknowledgements

We thank the staff and participants of the HWSC study for their important contribution. We also acknowledge the technical assistance provided by Jeny Flores-Morales (National Institute of Genomic Medicine, INMEGEN). In addition, the authors thank to the undergraduate students from the Biological Pharmaceutical Chemistry-UAM-X: Erica Mireya Mandujano Fernández and Mildred Carmona Santiago, for their participation in genotyping.

Funding

This project was partially supported by Consejo Nacional de Ciencia y Tecnología CF-2019-102962. The Health Workers Cohort Study was supported by: Consejo Nacional de Ciencia y Tecnología (Grant numbers: 7876, 87783, 262233, 26267 M, SALUD-2010-01-139796, SALUD-2011-01-161930, and CB-2013-01-221628).

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Authors and Affiliations

  1. Centro de Investigación en Políticas, Población y Salud de la Facultad de Medicina de la Universidad Nacional Autónoma de México (UNAM), Mexico City, México

    B. Rivera-Paredez & J. Salmerón

  2. Departamento de Genética, Instituto Nacional de Rehabilitación, Mexico City, México

    A. Hidalgo-Bravo

  3. Laboratorio de Genómica del Metabolismo Óseo, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, México

    G. León-Reyes & R. Velázquez-Cruz

  4. Laboratorio de Inmunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, México

    F. Barajas-Olmos, A. Martínez-Hernández & L. Orozco

  5. Centro de Investigación en Nutrición y Salud, Instituto Nacional de Salud Pública (INSP), Cuernavaca, Morelos, México

    E. Denova-Gutiérrez

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  1. B. Rivera-Paredez
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  2. A. Hidalgo-Bravo
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Contributions

Conceptualization and Investigation: B.R.-P. and R.V.-C.; Writing- original draft preparation: B.R.-P., R.V.-C., and A.H.-B.; Data Analysis: B.R.-P.; Writing—review and editing: B.R.-P., A.H.-B., G.L-R., E.D.-G., F.B.-O., A.M.-H., L.O., J.S. and R.V.-C.; Resources; R.V.-C, E.D.-G. and J.S; Data Curation: E.D.-G, J.S., F.B.-O., A.M.-H., L.O.; Funding acquisition: R.V.-C and J.S. All authors have read and agreed to the published version of the manuscript.

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Correspondence to R. Velázquez-Cruz.

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Rivera-Paredez, B., Hidalgo-Bravo, A., León-Reyes, G. et al. The role of single nucleotide variant rs3819817 of the Histidine Ammonia-Lyase gene and 25-Hydroxyvitamin D on bone mineral density, adiposity markers, and skin pigmentation, in Mexican population. J Endocrinol Invest 46, 1911–1921 (2023). https://doi.org/10.1007/s40618-023-02051-1

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