AHSG gene variant is associated with leanness among Swedish men

Hum Genet. 2005 Jun;117(1):54-60. doi: 10.1007/s00439-005-1286-z. Epub 2005 Apr 2.


Alpha(2) Heremans-Schmid glycoprotein (AHSG) is a plasma protein inhibiting the activity of the insulin receptor tyrosine kinase. Ahsg knock-out mice have increased insulin sensitivity and are resistant to diet-induced obesity. We hypothesized that functional variants of the AHSG gene segregating in the human population would reflect variation in body mass index (BMI). We genotyped 356 overweight or obese (BMI: 37.2 [25.0-66.5] kg/m(2)) and 148 lean (BMI: 23.7 [23.4-24.9] kg/m(2)) otherwise healthy Swedish men for three non-synonymous single-nucleotide polymorphisms (SNPs) within exon 6 (rs4917) and exon 7 (rs4918 and Arg299Cys) and one SNP in intron 1 (rs2593813) of the AHSG gene. The G/G genotype for rs2593813 was more common among lean than among obese and overweight individuals (odds ratio = 2.01, P = 0.009), whereas rs2593813 was in strong linkage disequilibrium (|D'| > or = 0.97) with rs4917 and rs4918. Homozygosity for the rs2593813:G-rs4917:Met-rs4918:Ser haplotype conferred an increased risk for leanness (odds ratio=1.90, P = 0.027). rs4917:Met and rs4918:Ser have previously been associated with lower AHSG protein level. A common variant of AHSG, previously associated with a lower AHSG protein level, is thus more common among lean than obese and overweight men, supporting the results from Ahsg knock-out mice, namely, that AHSG modulates body mass.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Blood Proteins / genetics*
  • Body Mass Index*
  • Case-Control Studies
  • Genotype
  • Humans
  • Linkage Disequilibrium
  • Male
  • Mice
  • Mice, Knockout
  • Middle Aged
  • Obesity / genetics*
  • Odds Ratio
  • Risk Factors
  • Sweden
  • alpha-2-HS-Glycoprotein


  • AHSG protein, human
  • Ahsg protein, mouse
  • Blood Proteins
  • alpha-2-HS-Glycoprotein