title: PNPLA3 polymorphisms and liver aminotransferase levels in a Mexican American population.
abstract: OBJECTIVE
  This study examined genetic associations of patatin-like phospholipase domain containing 3 gene (PNPLA3) polymorphisms and liver aminotransferases in an extensively documented, randomly recruited Mexican American population at high risk of liver disease.
  
  
  METHODS
  Two single nucleotide polymorphisms (SNP) in the PNPLA3 gene (i.e., rs738409 and rs2281135) were genotyped in 1532 individuals. Population stratification was corrected by the genotyping of 103 ancestry informative markers (AIMs) for Mexican Americans.
  
  
  RESULTS
  Both PNPLA3 SNPs showed highly significant association with alanine aminotransferase (ALT) levels, but was also, in males, associated with aspartate aminotransferase (AST) levels. Haplotypic association test of the two SNPs suggested stronger genetic association with rs738409 than rs2281135. Obvious sex effects were observed: rs738409-sex interaction in ALT levels P = 8.37 x 10(-4); rs738409-sex interaction in AST levels P = 5.03 x 10(-3).
  
  
  CONCLUSIONS
  This population study highlights a sex-specific association of PNPLA3 polymorphisms and elevated liver enzymes in a population-based study, independent of common pathological factors of the metabolic syndrome. The strong genetic association found in women ≤ 50 years old, but not in women > 50 years old, suggests that sex hormones may mediate the sex effect.
authors.affiliation: The University of Texas School of Public Health, Brownsville, TX 78520, USA.
authors.forename: Quan
authors.initials: Q
authors.lastname: Li
authors.forename: Hui-Qi
authors.initials: HQ
authors.lastname: Qu
authors.forename: Anne R
authors.initials: AR
authors.lastname: Rentfro
authors.forename: Megan L
authors.initials: ML
authors.lastname: Grove
authors.forename: Shaper
authors.initials: S
authors.lastname: Mirza
authors.forename: Yang
authors.initials: Y
authors.lastname: Lu
authors.forename: Craig L
authors.initials: CL
authors.lastname: Hanis
authors.forename: Michael B
authors.initials: MB
authors.lastname: Fallon
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Susan P
authors.initials: SP
authors.lastname: Fisher-Hoch
authors.forename: Joseph B
authors.initials: JB
authors.lastname: McCormick
mesh_terms: D000328:Adult; D000367:Age Factors; D000410:Alanine Transaminase / Q000235:genetics* / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D008049:Lipase / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008107:Liver Diseases / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D024821:Metabolic Syndrome / Q000235:genetics / Q000378:metabolism; D017058:Mexican Americans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012727:Sex Characteristics; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent