The shortness of Pygmies is associated with severe under-expression of the growth hormone receptor

The role of GHR and IGF1 genes in the genetic determination of African pygmies’ short stature

“…An eightfold under-expression of the GHR gene was previously found in pygmies, but no variation in the exons of the gene was found in 13 pygmies as compared to eight non-pygmies. 18 The three polymorphisms found in our study are located in the first intron of the gene, which had not been re-sequenced in this previous study. Our three height-associated SNPs may have a role in the expression of the gene or may be linked to an exonic functional polymorphism that was not identified in the smaller sample used in the previous study.…”

“…23,24 According to endocrinological assays, pygmy individuals have normal levels of GH but lower serum levels of IGF1, and exhibit an eightfold underexpression of the GHR gene as compared with the controls. 16,18,19 Therefore, the GHR and IGF1 genes represent good candidates to explain pygmies' short stature. We develop here a candidate-gene approach focusing on these two genes and on the signal transducers and activators of transcription STAT5A and STAT5B.…”

“…[13][14][15][16][17] Furthermore, a recent study showed that the expression of the GH receptor gene (GHR, which is the same gene as GHBP) is 8 times lower in pygmy subjects, as compared with neighboring non-pygmies. 18 Small regions of the GHR and IGF1 genes have been previously tested for association with the stature of African pygmies with negative results. [18][19][20][21] A recent genome-wide study has identified regions in the genome that might be involved in the difference in stature observed between pygmies from Cameroon and their non-pygmy neighbors, although this signal was not significant.…”

“…18 Small regions of the GHR and IGF1 genes have been previously tested for association with the stature of African pygmies with negative results. [18][19][20][21] A recent genome-wide study has identified regions in the genome that might be involved in the difference in stature observed between pygmies from Cameroon and their non-pygmy neighbors, although this signal was not significant. 22 Some of these regions contain genes linked to the GH-IGF1 signaling pathway.…”

Toward a comprehensive neurobiology of IGF‐I

“…In humans, serum levels of IGF-I are extraordinarily high, very steady, and widely different between individuals. There are environmental and genetic factors that account for these differences (Breese et al, 1991;Thissen et al, 1994;Adamo et al, 2006;Kappeler et al, 2008a,b;Bozzola et al, 2009), but these traits are not frequent among growth factors. While in mammals the main source of IGF-I is the liver (Yakar et al, 1999), all tissues produce this hormone/growth factor, and all types of cells express IGF-I receptors.…”