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PNPLA3 I148M polymorphism is associated with elevated alanine transaminase levels in Mexican Indigenous and Mestizo populations

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Abstract

The patatin like phospholipase domain-containing (PNPLA3) I148M variant is the strongest genetic factor associated with elevated alanine transaminase (ALT) levels in different populations, particularly in Hispanics who have the highest 148M risk allele frequency reported to date. It has been suggested that Indigenous ancestry is associated with higher ALT levels in Mexicans. The aim of the present study was to assess the frequency of the PNPLA3 148M risk allele in Mexican indigenous and Mestizo individuals, and to examine its association with serum ALT levels. The study included a total of 1624 Mexican individuals: 919 Indigenous subjects from five different native groups and 705 Mexican Mestizo individuals (141 cases with ALT levels ≥40 U/L and 564 controls with ALT <40 U/L). The I148M polymorphism was genotyped by TaqMan assays. The frequency of elevated ALT levels in Indigenous populations was 18.7 %, and varied according to obesity status: 14.4 % in normal weight, 19.9 % in overweight and 24.5 % in obese individuals. The Mexican indigenous populations showed the highest reported frequency of the PNPLA3 148M risk allele (mean 0.73). The M148M genotype was significantly associated with elevated ALT levels in indigenous individuals (OR = 3.15, 95 % CI 1.91–5.20; P = 7.1 × 10−6) and this association was confirmed in Mexican Mestizos (OR = 2.24, 95 % CI 1.50–3.33; P = 8.1 × 10−5). This is the first study reporting the association between M148M genotype and elevated ALT levels in Indigenous Mexican populations. The 148M allele risk may be considered an important risk factor for liver damage in Mexican indigenous and Mestizo populations.

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Abbreviations

PNPLA3 :

Patatin-like phospholipase domain-contain 3

NAFLD:

Non-alcoholic fatty liver disease

NASH:

Non-alcoholic steatohepatitis

ALT:

Alanine transaminase

AST:

Aspartate transaminases

IMSS:

Mexican Institute of Social Security

BMI:

Body mass index

HOMA-IR:

Homeostasis model assessment for insulin resistance

HDL-C:

High-density lipoprotein cholesterol

OR:

Odds ratio

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Acknowledgments

This research was supported by grant SALUD-2009-01-113861 from the Consejo Nacional de Ciencia y Tecnología (CONACyT). The study of the IMSS cohort is supported in part by grants from IMSS (FIS/IMSS/PROT/G12/1117) and CONACyT (26267M, SALUD-2008-01-87783 and SALUD-2011-C01-161930). PLM is in the Ciencias Bioquímicas PhD program from Universidad Nacional Autónoma de México (UNAM) and HVR is in the Ciencias Biológicas y de la Salud PhD program from Universidad Autónoma Metropolitana (UAM), and were supported by the PhD fellowships number 244112 and 234714 from CONACyT, México.

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Authors and Affiliations

  1. Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Mexico, Mexico

    Elena Larrieta-Carrasco

  2. Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, Universidad Nacional Autónoma de México (UNAM)-Instituto Nacional de Medicina Genómica (INMEGEN), Mexico, Mexico

    Victor Acuña-Alonzo, Paola León-Mimila, Hugo Villamil-Ramírez, Marta Menjivar & Samuel Canizales-Quinteros

  3. Laboratorio de Genética Molecular, Escuela Nacional de Antropología e Historia (ENAH), Mexico, Mexico

    Victor Acuña-Alonzo & Rodrigo Barquera-Lozano

  4. Laboratorio de Genómica del Metabolismo Óseo, INMEGEN, Mexico, Mexico

    Rafael Velázquez-Cruz & Vanessa Cárdenas

  5. Laboratorio de Genómica Computacional, INMEGEN, Mexico, Mexico

    Sandra Romero-Hidalgo

  6. Unidad de Investigación del Hígado, Fundación Médica Sur, Mexico, Mexico

    Nahúm Méndez-Sánchez

  7. Unidad de Investigación Epidemiológica y en Servicios de Salud, Instituto Mexicano del Seguro Social, Cuernavaca, Morelos, Mexico

    Manuel Bañuelos-Moreno, Yvonne N. Flores, Manuel Quiterio & Jorge Salmerón

  8. UCLA Department of Health Policy and Management, Fielding School of Public Health, Johnson Comprehensive Cancer Center, Los Angeles, CA, USA

    Yvonne N. Flores

  9. Centro de Investigación en Salud Poblacional, Instituto Nacional de Salud Pública, Cuernavaca, Mexico

    Jorge Salmerón

  10. Departamento de Inmunología, Instituto Nacional de Cardiología “Ignacio Chávez” (INCICh), Mexico, Mexico

    Fausto Sánchez-Muñoz

  11. Laboratorio de Enfermedades Cardiovasculares, INMEGEN, Mexico, Mexico

    Teresa Villarreal-Molina

  12. Departamento de Endocrinología y Metabolismo, INCMNSZ, Mexico, Mexico

    Carlos A. Aguilar-Salinas

Authors
  1. Elena Larrieta-Carrasco
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  2. Victor Acuña-Alonzo
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  3. Rafael Velázquez-Cruz
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  4. Rodrigo Barquera-Lozano
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  5. Paola León-Mimila
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  6. Hugo Villamil-Ramírez
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  7. Marta Menjivar
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  8. Sandra Romero-Hidalgo
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  10. Vanessa Cárdenas
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  11. Manuel Bañuelos-Moreno
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  12. Yvonne N. Flores
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  13. Manuel Quiterio
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  14. Jorge Salmerón
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  15. Fausto Sánchez-Muñoz
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  16. Teresa Villarreal-Molina
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  17. Carlos A. Aguilar-Salinas
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  18. Samuel Canizales-Quinteros
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Corresponding author

Correspondence to Samuel Canizales-Quinteros.

Additional information

Elena Larrieta-Carrasco and Victor Acuña-Alonzo have contributed equally to this study.

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Larrieta-Carrasco, E., Acuña-Alonzo, V., Velázquez-Cruz, R. et al. PNPLA3 I148M polymorphism is associated with elevated alanine transaminase levels in Mexican Indigenous and Mestizo populations. Mol Biol Rep 41, 4705–4711 (2014). https://doi.org/10.1007/s11033-014-3341-0

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