Pau Cindy T, Cheang Kai I, Modi Bhavi P, Kasippillai Thushiga, Keefe Candace C, Shulleeta Maria, Evans William S, Pal Lubna, Strauss Jerome F, Nestler John E, Welt Corrine K
Reproductive Endocrine Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
Departments of Obstetrics & Gynecology, Internal Medicine & Human & Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298, USA.
Pharmacogenomics. 2016 Nov;17(16):1765-1773. doi: 10.2217/pgs-2016-0079. Epub 2016 Oct 28.
Variants in genes encoding metformin transport proteins and the ATM gene are associated with metformin response. We hypothesized that these gene variants contribute to variable metformin treatment response in polycystic ovary syndrome.
MATERIALS & METHODS: The discovery cohort (n = 38) was studied in an open-label study. Results were replicated in two additional cohorts (n = 26 and n = 131). Response was assessed after 3-6 months of treatment with metformin extended-release 1500-2000 mg/day.
The rs683369 variant was associated with less weight loss in the discovery cohort (p = 0.003), but these results were not replicated (p = 0.8). There were no differences in glucose parameters, testosterone levels or ovulatory frequency as a function of genotype.
Variants in organic ion transporters do not explain the variable metformin response in polycystic ovary syndrome.
编码二甲双胍转运蛋白的基因和ATM基因中的变异与二甲双胍反应相关。我们推测这些基因变异导致多囊卵巢综合征患者二甲双胍治疗反应存在差异。
在一项开放标签研究中对发现队列（n = 38）进行了研究。结果在另外两个队列（n = 26和n = 131）中进行了重复验证。使用每日1500 - 2000毫克缓释二甲双胍治疗3 - 6个月后评估反应情况。
在发现队列中，rs683369变异与体重减轻较少相关（p = 0.003），但这些结果未得到重复验证（p = 0.8）。作为基因型的函数，血糖参数、睾酮水平或排卵频率没有差异。
有机离子转运体中的变异不能解释多囊卵巢综合征患者二甲双胍反应的差异。
