<italic>IRX3</italic> is a genetic modifier for birth weight, adolescent obesity and transaminase metabolism.

Summary: Objective: <italic>IRX3</italic> expression has been functionally associated in obesity‐associated long‐distance susceptibility loci, but the effect of the <italic>IRX3</italic> genetic variants on human obesity and obesity‐related metabolism remains uncertain. Methods: To determine the genetic role of <italic>IRX3</italic>, we conducted a molecular epidemiological analysis using three haplotype tagging single nucleotide polymorphisms (SNPs; rs8053360, rs3751723 and rs12445085) and one nonsynonymous SNP (rs1126960) at the <italic>IRX3</italic> locus in 333 junior and senior high school students from a northeast Chinese population. Results: We identified significant associations between <italic>IRX3</italic> SNPs and birth weight, body mass index (BMI), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and AST/ALT ratio. The rs8053360 CC and rs1126960 GG genotypes were associated with increased birth weight and BMI, especially in females. Individuals with the rs12445085 TT genotype had significantly higher levels of AST and ALT, whereas individuals with the rs1126960 GG genotype had a significantly lower AST/ALT ratio than did individuals with other genotypes. However, no significant relationships were found between any of the <italic>IRX3</italic> SNPs and metabolic syndrome or diabetes. Conclusions: <italic>IRX3</italic> genetic variants associate with birth weight, BMI and AST/ALT‐related transaminase metabolism, supporting the role of <italic>IRX3</italic> as an obesity‐associated susceptibility gene. [ABSTRACT FROM AUTHOR]