Diet and the frequency of the alanine:glyoxylate aminotransferase Pro11Leu polymorphism in different human populations

Caldwell, Elizabeth Frances and Mayor, Lianne and Thomas, Mark G. and Danpure, Christopher J. (2004) Diet and the frequency of the alanine:glyoxylate aminotransferase Pro11Leu polymorphism in different human populations. Human Genetics, 115 (6). pp. 504-509. ISSN 0340-6717

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Abstract

The intermediary metabolic enzyme alanine:glyoxylate aminotransferase (AGT) contains a Pro11Leu polymorphism that decreases its catalytic activity by a factor of three and causes a small proportion to be mistargeted from its normal intracellular location in the peroxisomes to the mitochondria. These changes are predicted to have significant effects on the synthesis and excretion of the metabolic end-product oxalate and the deposition of insoluble calcium oxalate in the kidney and urinary tract. Based on the evolution of AGT targeting in mammals, we have previously hypothesised that this polymorphism would be advantageous for individuals who have a meat-rich diet, but disadvantageous for those who do not. If true, the frequency distribution of Pro11Leu in different extant human populations should have been shaped by their dietary history so that it should be more common in populations with predominantly meat-eating ancestral diets than it is in populations in which the ancestral diets were predominantly vegetarian. In the present study, we have determined frequency of Pro11Leu in 11 different human populations with divergent ancestral dietary lifestyles. We show that the Pro11Leu allelic frequency varies widely from 27.9% in the Saami, a population with a very meat-rich ancestral diet, to 2.3% in Chinese, who are likely to have had a more mixed ancestral diet. F ST analysis shows that the differences in Pro11Leu frequency between some populations (particularly Saami vs Chinese) was very high when compared with neutral loci, suggesting that its frequency might have been shaped by dietary selection pressure.

Item Type:
Journal Article
Journal or Publication Title:
Human Genetics
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2700/2716
Subjects:
ID Code:
127829
Deposited By:
Deposited On:
28 Sep 2018 08:28
Refereed?:
Yes
Published?:
Published
Last Modified:
19 Aug 2020 04:49