Association of the Estrogen Receptor 1 (ESR1) Gene with Body Height in Adult Males from Two Swedish Population Cohorts

Abstract

Human body height is a complex genetic trait with high heritability. We performed an association study of 17 candidate genes for height in the Uppsala Longitudinal Study of Adult Men (ULSAM) that consists of 1153 elderly men of age 70 born in the central region of Sweden. First we genotyped a panel of 137 single nucleotide polymorphism (SNPs) evenly distributed across the candidate genes in the ULSAM cohort. We identified 4 SNPs in the estrogen receptor gene (ESR1) on chromosome 6q25.1 with suggestive signals of association (p<0.05) with standing body height. This result was followed up by genotyping the same 25 SNPs in the ESR1 gene as in ULSAM in a second population cohort, the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort that consist of 507 males and 509 females of age 70 from the same geographical region as ULSAM. One SNP, rs2179922 located in intron 4 of ESR1 showed and association signal (p = 0.0056) in the male samples from the PIVUS cohort. Homozygote carriers of the G-allele of the SNP rs2179922 were on average 0.90 cm taller than individuals with the two other genotypes at this SNP in the ULSAM cohort and 2.3 cm taller in the PIVUS cohort. No association was observed for the females in the PIVUS cohort.

Genetic Polymorphisms Associated with Idiopathic Short Stature and First-Year Response to Growth Hormone Treatment

“…The ESR1 rs2234693 polymorphism (PVUII intron 1) has been linked to height during puberty [31, 32] and adulthood [33, 34]. Furthermore, recessive germline ESR1 mutations causing estrogen resistance and marked pubertal growth delays have been reported in 2 unrelated patients [35, 36]. Our finding of a significantly lower prevalence of the “tall” (C) allele at rs2234693 in our ISS cohort compared with controls (odds ratio 0.50, 95% CI 0.25–0.98) provides independent evidence for an association between ERα and stature, suggesting that variations in estrogen sensitivity may contribute to the impaired growth that characterizes ISS.…”

Polymorphisms in CYP17, COMT, and ESR1 genes in women after menopause and association with bone mineral density

“…These sites were associated with low bone mass and low estradiol levels, and it is likely that the allele exerts its influence on the bone in early adulthood, leading to an increased risk of osteoporosis later in life (Jeedigunta et al, 2010). rs9322331 was recently genotyped in an Uppsala Longitudinal Study of Adult Men cohort by Dahlgren et al (2008), indicating an association between ESR1 and body height in adults males (P = 0.040). In this study, we found a significant association between the polymorphism and osteopenia development (P = 0.046).…”

Genetic Variation in Candidate Genes Like the HMGA2 Gene in the Extremely Tall

“…We genotyped 10 candidate gene polymorphisms using published primers and protocols. Brief descriptions are given below for polymorphisms in the genes for luteinizing hormone-beta (LHB) [16], cytochrome P450c17α (CYP17) [17], CYP19 [10,11], ESR1 [7,8,9], PTH/PTHrP receptor (PTHR1) [18,19], VDR [12,13], collagen type Iα1 (COLIα1) [20,21], catechol- O -methyltransferase (COMT) [22,23], HMGA2 [14], and peroxisome proliferator-activated receptor-γ 3 (PPARγ3) [24]. All assays were run in duplicate to detect possible genotyping errors.…”

“…Estrogens play a crucial role in the timing of cessation of longitudinal bone growth [6]. Estrogen receptor-α gene (ESR1) polymorphisms have been studied extensively in relation to bone mineral density and have been associated with height variation [7,8,9]. Aromatase catalyzes the rate-limiting step in the conversion of androgens to estrogens.…”