Polymorphisms in adiposity-related genes are associated with age at menarche and menopause in breast cancer patients and healthy women

Abstract

Four SNPs (rs2167270 of LEP, rs7602 of LEPR and rs4684846 and rs3856806 of PPARγ) were associated with late menarche (≥ 17-year-old). Four SNPs (rs2167270 of LEP and rs1801282, rs2120825, and rs3856806 of PPARγ) were associated with early menopause (<40-year-old) among post-menopausal women. In logistic regression models with covariate adjustment, women with the GG genotype of rs7602 (LEPR) had a higher risk for late menarche [odds ratio (OR) = 1.83, 95% confidence interval (CI) = 1.01-3.31] compared with their counterparts carrying the GA or AA genotypes. In addition, the GG genotype of rs2167270 (LEP) was inversely associated with a duration of menstruation of <30 years (OR = 0.59, 95% CI = 0.31-1.00) compared with the GA or AA genotypes. BIAS, LIMITATIONS AND GENERALIZABILITY TO OTHER POPULATIONS: We obtained information on the age at menarche and menopause from self-administered questionnaires, and some participants might have had difficulty in remembering their age at menarche and menopause. However, this is a non-differential misclassification and should not appreciably affect the interpretation of the results of this study.

Descriptive review: Hormonal influences on risk for eating disorder symptoms during puberty and adolescence

“…Cholecystokinin is peptide hormone produced in the small intestine that serves as a peripheral satiety signal, and the CCK satiety signal is a key mechanism mediating the effects of estradiol on food intake . Lastly, variants of LEP, which codes for the production of leptin and plays a role in food intake and satiety, have been correlated with ages of menarche and menopause, and duration of menstrual cycles . It should be noted, however, that genetic research on EDs, like other complex behavioral phenotypes, has been plagued by frequent failures to replicate associations.…”

“…5 Lastly, variants of LEP, which codes for the production of leptin and plays a role in food intake and satiety, have been correlated with ages of menarche and menopause, and duration of menstrual cycles. 18 It should be noted, however, that genetic research on EDs, like other complex behavioral phenotypes, has been plagued by frequent failures to replicate associations. The failure to identify all the specific polymorphisms underlying genetic influence on EDs (the "missing heritability" problem) may be due to low statistical power, the effects of rare genetic variants, and gene 3 gene or gene 3 environment interactions.…”

Genomic Markers of Ovarian Reserve

“…173 SNPs within the PPARG gene were significantly associated with age at menopause in Caucasian (GWAS) and Korean populations but not African American women (targeted genotyping and GWAS). 96,97,174 Pparg / mice die in utero due to placental defects. 175 Elimination of Pparg specifically in granulosa cells and oocytes caused infertility or subfertility in one-third of females due to implantation deficiencies as follicle numbers and ovulated oocytes did not differ from controls 176 (Fig.…”

Peroxisome proliferator-activated receptor γ2 Pro12Ala (rs1801282) polymorphism and breast cancer susceptibility: A meta-analysis

“…Another study that lacked the full text was also excluded (31). Therefore, four individual studies remained for further analysis (19)(20)(21)(22). A total of 2,279 cases and 2,360 controls available from the included reports for the PPAR-γ2 Pro 12 Ala polymorphism information were obtained.…”

“…Numerous studies have also been conducted to estimate the association between the Pro 12 Ala (rs1801282) polymorphism in the PPAR-γ2 gene and the risk of breast cancer, however the results have not always been consistent (19)(20)(21)(22).…”