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 (
> 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.
We studied the possible effects of climatic factors on the world distribution of alleles determining alpha 2-HS-glycoprotein (AHSG) phenotypes in human populations. New data on AHSG polymorphism in certain ethnic groups of Russia are presented. All available data on the distribution of AHSG gene frequencies in the world (number of populations n = 51) were used to analyze possible correlations between AHSG*2 allele frequencies and seven climatic-geographic parameters. A strong positive correlation was found between AHSG*2 allele frequency and geographic latitude of territories inhabited by the study populations (r = 0.814). The dependence of the AHSG*2 allele distribution in the world on the intensity of ultraviolet radiation (400-315 nm) was estimated at r = -0.826. Such climatic characteristics as the total amount of insolation and the average annual temperature proved to make equal contributions to variation in AHSG*2 allele frequency (r = -0.683 and -0.658, respectively). A computer cartographic model of the AHSG*2 allele distribution in the Old World populations of the Northern Hemisphere was constructed.