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CONTEXT Approximately 70% of women report experiencing vasomotor symptoms (VMS, hot flashes and/or night sweats). The etiology of VMS is not clearly understood but may include genetic factors. EVIDENCE ACQUISITION We searched PubMed and Embase in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. We included studies on associations between genetic variation and VMS. We excluded studies focused on medication interventions or prevention or treatment of breast cancer. EVIDENCE SYNTHESIS Of the 202 unique citations, 18 citations met the inclusion criteria. Study sample sizes ranged from 51 to 17,695. Eleven of the 18 studies had fewer than 500 participants; two studies had ≥ 1,000. Overall, statistically significant associations with VMS were found for variants in 14 of the 26 genes assessed in candidate gene studies. The cytochrome P450 family 1 subfamily A member 1 (CYP1B1) gene was the focus of the largest number (n = 7) of studies, but strength and statistical significance of associations of CYP1B1 variants with VMS were inconsistent. A genome-wide association study reported statistically significant associations between 14 single-nucleotide variants in the tachykinin receptor 3 gene and VMS. Heterogeneity across trials regarding VMS measurement methods and effect measures precluded quantitative meta-analysis; there were few studies of each specific genetic variant. CONCLUSIONS Genetic variants are associated with VMS. The associations are not limited to variations in sex steroid metabolism genes. However, studies were few and future studies are needed to confirm and extend these findings.
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The_Journal_of_clinical_endocrinology_and_metabolism
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Genetic variation and hot flashes: A systematic review.
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