|
|||||
|
|
PNPLA3 I148M polymorphism is associated with elevated alanine transaminase levels in Mexican Indigenous and Mestizo populations |
|
| Authors: | Elena Larrieta-Carrasco Victor Acuña-Alonzo Rafael Velázquez-Cruz Rodrigo Barquera-Lozano Paola León-Mimila Hugo Villamil-Ramírez Marta Menjivar Sandra Romero-Hidalgo Nahúm Méndez-Sánchez Vanessa Cárdenas Manuel Bañuelos-Moreno Yvonne N. Flores Manuel Quiterio Jorge Salmerón Fausto Sánchez-Muñoz Teresa Villarreal-Molina Carlos A. Aguilar-Salinas Samuel Canizales-Quinteros |
| Affiliation: | 1. Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Mexico, Mexico 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 3. Laboratorio de Genética Molecular, Escuela Nacional de Antropología e Historia (ENAH), Mexico, Mexico 4. Laboratorio de Genómica del Metabolismo óseo, INMEGEN, Mexico, Mexico 5. Laboratorio de Genómica Computacional, INMEGEN, Mexico, Mexico 6. Unidad de Investigación del Hígado, Fundación Médica Sur, Mexico, Mexico 7. Unidad de Investigación Epidemiológica y en Servicios de Salud, Instituto Mexicano del Seguro Social, Cuernavaca, Morelos, Mexico 8. UCLA Department of Health Policy and Management, Fielding School of Public Health, Johnson Comprehensive Cancer Center, Los Angeles, CA, USA 9. Centro de Investigación en Salud Poblacional, Instituto Nacional de Salud Pública, Cuernavaca, Mexico 10. Departamento de Inmunología, Instituto Nacional de Cardiología “Ignacio Chávez” (INCICh), Mexico, Mexico 11. Laboratorio de Enfermedades Cardiovasculares, INMEGEN, Mexico, Mexico 12. Departamento de Endocrinología y Metabolismo, INCMNSZ, Mexico, Mexico |
| 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. |
| Keywords: | |
| 本文献已被 SpringerLink 等数据库收录！ | |