Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
Eur J Obstet Gynecol Reprod Biol. 2012 Dec;165(2):302-6. doi: 10.1016/j.ejogrb.2012.07.024. Epub 2012 Aug 15.
To determine whether fat mass and obesity-associated gene polymorphisms rs9939609 T>A and rs8050136 A>C or their haplotypes influence anthropometric and metabolic variables in recently postmenopausal women receiving hormone therapy.
In this randomized crossover study carried out in a university clinic, 86 postmenopausal women consulting for symptoms of estrogen deficiency were genotyped by real-time polymerase chain reaction for single nucleotide polymorphisms rs9939609 T>A and rs8050136 A>C of the fat mass and obesity-associated gene. Haplotypes were constructed from the combination of polymorphisms rs9939609 and rs8050136, and their frequencies were inferred using the PHASE 2.1.1 program. Participants were clinically evaluated before and after 6 months of hormone therapy to determine body mass index (current kg/m(2)) and waist circumference, blood pressure, lipid profile (total cholesterol, HDL cholesterol and triglycerides) plasma glucose (oral glucose tolerance test), and insulin. Blood samples were also drawn for ultra sensitive C reactive protein. The lipid accumulation product index was calculated as (waist [cm] - 58) × triglyceride concentration (mmol/L). Non-normally distributed parameters were log10 transformed before statistical analysis. Measurements at baseline and at follow-up were compared with ANOVA for repeated measures. Data were considered significant at P<0.05.
In women with the homozygous polymorphic AA genotype of the single nucleotide polymorphisms rs9939609 and the wild AA genotype of the single nucleotide polymorphisms rs8050136, lipid accumulation product index and ultra sensitive C reactive protein were higher before hormone therapy in comparison with women with other genotypes from the same single nucleotide polymorphisms group. There was no worsening of any of the anthropometric or metabolic variables, and lipid accumulation product index improved slightly after hormone therapy in SNP rs9939609 (P=0.03) and haplotype AAAA. No changes were observed after hormone therapy in SNP rs8050136.
The presence of fat mass and obesity-associated gene risk variants in healthy early postmenopausal women does not adversely affect their response to hormone therapy.
确定脂肪量和肥胖相关基因多态性 rs9939609 T>A 和 rs8050136 A>C 或其单倍型是否会影响正在接受激素治疗的近期绝经后女性的人体测量和代谢变量。
在大学诊所进行的这项随机交叉研究中，对 86 名因雌激素缺乏症状就诊的绝经后女性进行了实时聚合酶链反应基因分型，检测脂肪量和肥胖相关基因的单核苷酸多态性 rs9939609 T>A 和 rs8050136 A>C。单倍型由多态性 rs9939609 和 rs8050136 的组合构建，并使用 PHASE 2.1.1 程序推断其频率。参与者在激素治疗前和治疗后 6 个月进行临床评估，以确定体重指数（当前 kg/m(2)）和腰围、血压、血脂谱（总胆固醇、高密度脂蛋白胆固醇和甘油三酯）、血浆葡萄糖（口服葡萄糖耐量试验）和胰岛素。还抽取了血液样本用于超敏 C 反应蛋白检测。脂质积累产物指数计算为（腰围[cm]-58）×甘油三酯浓度（mmol/L）。非正态分布参数在进行统计分析前进行了对数转换。使用重复测量方差分析比较基线和随访时的测量值。数据在 P<0.05 时被认为具有统计学意义。
在单核苷酸多态性 rs9939609 的纯合多态性 AA 基因型和单核苷酸多态性 rs8050136 的野生 AA 基因型的女性中，与来自同一单核苷酸多态性组的其他基因型的女性相比，在接受激素治疗之前，脂质积累产物指数和超敏 C 反应蛋白更高。在 SNP rs9939609（P=0.03）和单倍型 AAAA 中，接受激素治疗后，任何人体测量或代谢变量均未恶化，脂质积累产物指数略有改善。在 SNP rs8050136 中，激素治疗后没有观察到变化。
在健康的早期绝经后女性中，脂肪量和肥胖相关基因的风险变异不会对其对激素治疗的反应产生不利影响。
