title: PNPLA3 I148M polymorphism is associated with elevated alanine transaminase levels in Mexican Indigenous and Mestizo populations.
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.
authors.affiliation: Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Mexico, Mexico.
authors.forename: Elena
authors.initials: E
authors.lastname: Larrieta-Carrasco
authors.forename: Victor
authors.initials: V
authors.lastname: Acuña-Alonzo
authors.forename: Rafael
authors.initials: R
authors.lastname: Velázquez-Cruz
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Barquera-Lozano
authors.forename: Paola
authors.initials: P
authors.lastname: León-Mimila
authors.forename: Hugo
authors.initials: H
authors.lastname: Villamil-Ramírez
authors.forename: Marta
authors.initials: M
authors.lastname: Menjivar
authors.forename: Sandra
authors.initials: S
authors.lastname: Romero-Hidalgo
authors.forename: Nahúm
authors.initials: N
authors.lastname: Méndez-Sánchez
authors.forename: Vanessa
authors.initials: V
authors.lastname: Cárdenas
authors.forename: Manuel
authors.initials: M
authors.lastname: Bañuelos-Moreno
authors.forename: Yvonne N
authors.initials: YN
authors.lastname: Flores
authors.forename: Manuel
authors.initials: M
authors.lastname: Quiterio
authors.forename: Jorge
authors.initials: J
authors.lastname: Salmerón
authors.forename: Fausto
authors.initials: F
authors.lastname: Sánchez-Muñoz
authors.forename: Teresa
authors.initials: T
authors.lastname: Villarreal-Molina
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Aguilar-Salinas
authors.forename: Samuel
authors.initials: S
authors.lastname: Canizales-Quinteros
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000235:genetics* / Q000378:metabolism; D000483:Alleles; D005234:Fatty Liver / Q000150:complications / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007199:Indians, South American; D008049:Lipase / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D011110:Polymorphism, Genetic; D044382:Population Groups; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D000410:Alanine Transaminase; D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent