Sunday, September 19, 2010


Developmental programming of growth: Genetic variant in GH2 gene encoding placental growth hormone contributes to adult height determination.

"Given the physiological role of placental growth hormone (PGH) during intrauterine development and growth, genetic variation in the coding Growth hormone 2 (GH2) gene may modulate developmental programming of adult stature. Two major GH2 variants were described worldwide, determined by single polymorphism (rs2006123; c.171 + 50C > A).
Significant association of GH2 rs2006123 with height. No association was detected with BMI. Notably, rs2006123 was in strong LD (r2 ≥ 0.87) with SNPs significantly associated with height (rs2665838, rs7209435, rs11658329) and mapped near GH2 in three independent meta-analyses of GWA studies."

"In most mammals, a single GH1 gene encodes the pituitary growth hormone (GH), whereas in primates, novel placenta-specific GH-related genes have arisen through gene duplications. In humans, GH/CSH cluster consists of five highly homologous (91–97%) and structurally similar genes: GH1, GH2, CSH1, CSH2 and CSHL1 (chorionic somatomammotropin-like 1)"

"Significantly lower placental expression of GH2 and reduced levels of circulating PGH have been reported in women with fetal intrauterine growth retardation/small-for-gestational-age pregnancies"

"given the physiological role of PGH during intrauterine development, the genetic variation in the GH2 gene may modulate growth in utero and in early infancy, therefore possibly affecting the developmental programming of human stature in adulthood."

"he effect of the A-variant was detected 0.45 cm per allele and 1.26 cm for the AA-genotype; whereas among men (n = 1679) the A-allele carrier effect was 0.86 cm per allele and 1.47 cm for AA-homozygotes."

"PGH secreted by syncytiotrophoblast functions as an insulin antagonist, controls maternal Insulin Growth Factor 1 (IGF-1) production and glucose utilization in pregnancy. The induction of PGH by glucose deprivation provides a feedback loop to ensure a delivery of nutrients to developing fetus."

"transgenic mice over-expressing the gene encoding for PGH became larger than their normal littermates and they are at risk to develop insulin resistance in later life"

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