title: Developmental programming of growth: genetic variant in GH2 gene encoding placental growth hormone contributes to adult height determination.
abstract: BACKGROUND
  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). We sought to study whether GH2 variants may contribute to adult anthropometric measurements.
  
  
  METHODS
  Genotyping of GH2 SNP rs2006123 by RFLP, testing its genetic association with adult height and Body Mass Index (BMI) by linear regression analysis, and combining the results of three individual study samples in meta-analysis.
  
  
  METHODS
  HYPEST (Estonia), n = 1464 (506 men/958 women), CADCZ (Czech), n = 871 (518/353); UFA (Bashkortostan), n = 954 (655/299); meta-analysis, n = 3289 (1679/1610).
  
  
  RESULTS
  Meta-analysis across HYPEST, CADCZ and UFA samples (n = 3289) resulted in significant association of GH2 rs2006123 with height (recessive model: AA-homozygote effect: beta (SE) = 1.26 (0.46), P = 5.90 × 10⁻³; additive model: A-allele effect: beta (SE) = 0.45 (0.18), P = 1.40 × 10⁻²). Among men (n = 1679), the association of the A-allele with taller stature remained significant after multiple-testing correction (additive effect: beta = 0.86 (0.28), P = 1.83 × 10⁻³). 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.
  
  
  CONCLUSIONS
  This is the first study demonstrating a link between a placental gene variant and programming of growth potential in adulthood. The detected association between PGH encoding GH2 and adult height promotes further research on the role of placental genes in prenatal programming of human metabolism.
authors.affiliation: Human Molecular Genetics Group, Institute of Molecular and Cell Biology, University of Tartu, Riia St. 23, Tartu 51010, Estonia; Institute of Biochemistry and Genetics, Ufa Scientific Centre of Russian Academy of Sciences, Ufa, Russia.
authors.forename: Y
authors.initials: Y
authors.lastname: Timasheva
authors.forename: M
authors.initials: M
authors.lastname: Putku
authors.forename: R
authors.initials: R
authors.lastname: Kivi
authors.forename: V
authors.initials: V
authors.lastname: Kožich
authors.forename: J
authors.initials: J
authors.lastname: Männik
authors.forename: M
authors.initials: M
authors.lastname: Laan
mesh_terms: D000328:Adult; D000368:Aged; D001486:Bashkiria; D001827:Body Height; D015992:Body Mass Index; D001846:Bone Development; D018153:Czech Republic; D004957:Estonia; D005260:Female; D047109:Fetal Development; D005787:Gene Frequency; D056726:Genetic Association Studies; D013006:Growth Hormone / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D010926:Placental Hormones / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy
chemical_list: C064980:GH2 protein, human; D010926:Placental Hormones; D013006:Growth Hormone
keywords: Association study; Developmental programming; GH2 gene; Human height and BMI; Placental growth hormone; Polymorphism
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