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Genetic risk of SNPs in the estrogen receptors was analyzed by a case\u2013control study. The interaction between gene and environmental factors for osteoporosis were assessed by a case\u2010only design. Significant increases in osteoporosis risk were observed with minor alleles of rs2077647 located in the first exon and rs2234693 located in the first intron of estrogen receptor \u03b1 (ESR\u03b1). Haplotype CC at these risk SNPs was strongly associated with osteoporosis risk (odds ratio [OR]\u2009=\u20093.15, 95% confidence interval [CI]\u2009=\u20091.83\u20135.41). There was a statistically significant interaction between haplotype CC and alcohol drinking; moderate alcohol consumption decreased genetic risk of osteoporosis (OR\u2009=\u20090.22, 95%CI\u2009=\u20090.05\u20130.83). \u00a9 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. 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