Causal Association of Haptoglobin With Obesity in Mexican Children: A Mendelian Randomization Study

Author:

Vázquez-Moreno Miguel12,Locia-Morales Daniel13,Perez-Herrera Aleyda4,Gomez-Diaz Rita A5,Gonzalez-Dzib Roxana6,Valdez-González Adriana L5,Flores-Alfaro Eugenia3,Corona-Salazar Perla1,Suarez-Sanchez Fernando1,Gomez-Zamudio Jaime1,Valladares-Salgado Adan1,Wacher-Rodarte Niels5,Cruz Miguel1,Meyre David27ORCID

Affiliation:

1. Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI del Instituto Mexicano del Seguro Social, Mexico City, Mexico

2. Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada

3. Laboratorio de Investigación en Epidemiología Clínica y Molecular, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, 39090, Mexico

4. Consejo Nacional de Ciencia y Tecnología, Instituto Politécnico Nacional-Centro Interdisciplinario de Investigación para el Desarrollo Integral-Regional Unidad Oaxaca, Oaxaca, Mexico

5. Unidad de Investigación en Epidemiología Clínica, Hospital de Especialidades Bernardo Sepúlveda, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México

6. Servicio de Prestaciones Médicas del Instituto Mexicano del Seguro Social, Delegación Campeche, Campeche, Mexico

7. Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada

Abstract

Abstract Context Little is known about the association between haptoglobin level and cardiometabolic traits. A previous genome-wide association study identified rs2000999 in the HP gene as the stronger genetic contributor to serum haptoglobin level in European populations. Objective and Design We investigated the association of HP rs2000999 with serum haptoglobin and childhood and adult obesity in up to 540/697 and 592/691 Mexican cases and controls, respectively. Anthropometric and biochemical data were collected. Serum haptoglobin was measured by an immunoturbidimetry assay. HP rs2000999 was genotyped using the TaqMan technology. Mendelian randomization analysis was performed using the Wald and inverse variance weighting methods. Results Haptoglobin level was positively associated with childhood and adult obesity. HP rs2000999 G allele was positively associated with haptoglobin level in children and adults. HP rs2000999 G allele was positively associated with childhood but not adult obesity. The association between HP rs2000999 and childhood obesity was removed after adjusting for haptoglobin level. In a Mendelian randomization analysis, haptoglobin level genetically predicted by HP rs2000999 showed a significant causal effect on childhood obesity by the Wald and inverse variance weighting methods. Conclusion Our data provide evidence for the first time for a causal positive association between serum haptoglobin level and childhood obesity in the Mexican population. Our study contributes to the genetic elucidation of childhood obesity and proposes haptoglobin as an important biomarker and treatment target for obesity.

Funder

Instituto Mexicano del Seguro Social

Priority Health Topics 2017

Universidad Nacional Autónoma de México

Universidad Autónoma de Guerrero

Consejo Nacional de Ciencia y Tecnología

Canada Research Chair in Genetics of Obesity

Publisher

The Endocrine Society

Subject

Biochemistry (medical),Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

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