ArticleMenopause (New York, N.Y.)2015
A potentially functional variant in the serotonin transporter gene is associated with premenopausal and perimenopausal hot flashes.
Article in Menopause (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
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Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.
- Genetic Variation and Hot Flashes: A Systematic Review.The Journal of clinical endocrinology and metabolism · 2020Pooled it
- Ojayeonjonghwan, an oriental medicine composed of five seeds, protects against vasomotor and neurological disorders in estrogen-deficient rats.Experimental biology and medicine (Maywood, N.J.) · 2019Article
- Intermittent fasting protects against the deterioration of cognitive function, energy metabolism and dyslipidemia in Alzheimer's disease-induced estrogen deficient rats.Experimental biology and medicine (Maywood, N.J.) · 2018Article
- Looking Beyond the 5-HTTLPR Polymorphism: Genetic and Epigenetic Layers of Regulation Affecting the Serotonin Transporter Gene Expression.Molecular neurobiology · 2017Review
- Association of genetic variation in the tachykinin receptor 3 locus with hot flashes and night sweats in the Women's Health Initiative Study.Menopause (New York, N.Y.) · 2017Observational
- The Midlife Women's Health Study - a study protocol of a longitudinal prospective study on predictors of menopausal hot flashes.Women's midlife health · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveAn increase in the use of selective serotonin reuptake inhibitors (SSRIs) and/or serotonin-norepinephrine reuptake inhibitors (SNRIs) to relieve menopausal hot flashes (HFs) has been observed recently. However, response to them has been heterogeneous. We hypothesized that this heterogeneity might be partially attributed to genetic variations in genes encoding the serotonin and/or norepinephrine transporters (SLC6A4 and SLC6A2). As a first step in testing the role of genetics in response to SSRIs/SNRIs, we examined the association between HFs and genetic variants within these two genes.
methodsWe tested 29 haplotype-tagging single nucleotide polymorphisms within SLC6A4 and SLC6A2 for their association with HFs separately for European-American (396 cases and 392 controls) and African-American (125 cases and 81 controls) premenopausal and perimenopausal women.
resultsWe found that the minor allele of SLC6A4_rs11080121 was associated with protection against HFs (odds ratio, 0.75; 95% CI, 0.60-0.94) only in European-American women. Bioinformatics analyses indicated that rs11080121 is fully correlated with rs1042173 in the 3' untranslated region of SLC6A4. The minor allele of rs1042173 seems to disrupt a conserved binding site for hsa-miR-590-3p microRNA.
conclusionsDisruption of a microRNA binding site leads to higher expression of SLC6A4, higher expression of SLC6A4 leads to depletion of serotonin in synaptic clefts, and depletion of serotonin triggers the presynaptic autoreceptor feedback mechanism to produce more serotonin, which is protective against HFs. This is the first study to test the association between HFs in both European-American and African-American premenopausal and perimenopausal women and genetic variants in two neurotransmitter transporter genes, SLC6A2 and SLC6A4. This information can be used in tailoring the pharmaceutical use of SSRIs/SNRIs for HF relief.
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