MC4R 变异 rs12970134 和 rs17782313 与沙特阿拉伯西部地区肥胖型多囊卵巢综合征患者相关。
MC4R variants rs12970134 and rs17782313 are associated with obese polycystic ovary syndrome patients in the Western region of Saudi Arabia.
机构信息
Biochemistry Department, King Abdulaziz University, P.O. Box 80218, Abdullah Sulayman St., Jeddah, 21589, Saudi Arabia.
Centre of Innovation in Personalized Medicine, King Abdulaziz University, P.O. Box 80216, Jeddah, Saudi Arabia.
出版信息
BMC Med Genet. 2019 Aug 20;20(1):144. doi: 10.1186/s12881-019-0876-x.
BACKGROUND
Polycystic ovary syndrome (PCOS) is a common endocrine disorder causing infertility in reproductive-age women. The cause of PCOS is not fully understood but it is thought to be influenced by environmental and genetic factors. Obesity is greatly related to PCOS and its reduction is one of the major aims in treating PCOS. Melanocortin 4 receptor (MC4R) gene polymorphisms were detected to be associated with different levels of obesity. Therefore, we aimed to determine the genotype and allele frequency of MC4R variants rs12970134 (A/G) and rs17782313 (C/T) in PCOS and investigate their association with PCOS and its clinical variables.
METHODS
A case-control study was conducted on 189 women, consisting of 95 PCOS cases and 94 controls. Genotyping was performed by real-time polymerase chain reaction (PCR) using TaqMan™ Genotyping assays. Quantitative data were presented as (median ± interquartile range (IQR) whereas qualitative data were presented as frequencies. The chi-squared test was used to observe the difference between SNPs within the study groups (PCOS and control subjects). Multinomial logistic regression was used to test the risk of obesity and development of PCOS considering p < 0.05 is statistically significant.
RESULTS
Rs12970134 and rs17782313 are significantly associated with body mass index (BMI, kg/m, p < 0.0001) in PCOS women but not associated with PCOS itself. Risk alleles in our population are A in rs12970134 and C in rs17782313 that are associated with high BMI (> 30 kg/m) in obese women with PCOS (OR = 1.348, p = 0.002 and OR = 1.364, p = 0.002 respectively) in the homozygous state. In addition, we found that the other genotypes for non-obese PCOS group, AG/GG for rs12970134 and CT/TT for rs17782313, are associated with hirsutism, loss of hair, hyperandrogenism and anti-Müllerian hormone in PCOS.
CONCLUSIONS
These findings demonstrate that MC4R single nucleotide polymorphisms, rs12970134 and rs17782313, are correlated with elevated BMI in PCOS but are not causative factors for PCOS among women in the western region of Saudi Arabia. Moreover, the reverse genotypes are associated with major clinical variants in non-obese (< 30 kg/m) PCOS patients may demonstrate a poor prognosis for this group.
背景
多囊卵巢综合征（PCOS）是一种常见的内分泌疾病，可导致育龄妇女不孕。PCOS 的病因尚未完全阐明，但据认为与环境和遗传因素有关。肥胖与 PCOS 密切相关，降低体重是治疗 PCOS 的主要目标之一。黑皮质素 4 受体（MC4R）基因多态性与不同程度的肥胖有关。因此，我们旨在确定 PCOS 患者 MC4R 变体 rs12970134（A/G）和 rs17782313（C/T）的基因型和等位基因频率，并研究它们与 PCOS 及其临床变量的关系。
方法
对 189 名女性进行病例对照研究，其中 95 名 PCOS 患者和 94 名对照。采用 TaqMan™ 基因分型试剂盒通过实时聚合酶链反应（PCR）进行基因分型。定量数据以中位数±四分位距（IQR）表示，定性数据以频率表示。卡方检验用于观察研究组（PCOS 和对照组）中 SNP 之间的差异。多变量逻辑回归用于检验肥胖和 PCOS 发展的风险，考虑到 p<0.05 具有统计学意义。
结果
rs12970134 和 rs17782313 与 PCOS 女性的体重指数（BMI，kg/m）显著相关（p<0.0001），但与 PCOS 本身无关。我们人群中的风险等位基因是 rs12970134 中的 A 和 rs17782313 中的 C，它们与肥胖的 PCOS 女性中高 BMI（>30 kg/m）相关（OR=1.348，p=0.002 和 OR=1.364，p=0.002）在纯合状态下。此外，我们发现非肥胖 PCOS 组的其他基因型，rs12970134 的 AG/GG 和 rs17782313 的 CT/TT，与 PCOS 中的多毛症、脱发、高雄激素血症和抗苗勒氏管激素有关。
结论
这些发现表明，MC4R 单核苷酸多态性 rs12970134 和 rs17782313 与 PCOS 中 BMI 的升高相关，但在沙特阿拉伯西部地区的女性中并非 PCOS 的致病因素。此外，相反的基因型与非肥胖（<30 kg/m）PCOS 患者的主要临床变异相关，这可能表明该组预后不良。
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