科研之友
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摘要
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'| >= 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.
- 出版日期2005-6
