Siddamalla Swapna, Reddy Tumu Venkat, Govatati Suresh, Guruvaiah Praveen, Deenadayal Mamata, Shivaji Sisinthy, Bhanoori Manjula
Department of Biochemistry, Osmania University, Hyderabad, India.
Infertility Institute and Research Centre (IIRC), Secundrabad, India.
Eur J Obstet Gynecol Reprod Biol. 2018 Aug;227:13-18. doi: 10.1016/j.ejogrb.2018.05.027. Epub 2018 May 24.
Polycystic Ovary Syndrome (PCOS) is a heterogeneous multifactorial endocrine metabolic disorder. In addition to hyperandrogenism, acne, hirsutism, obesity, oligoanovulation and infertility, insulin resistance is also a common feature in women of PCOS. Tumor suppressor genes (TSGs) perform essential function in the maintenance of genomic stability and regulatory pathways influencing the activity of several replication and transcription factors. The main aim of this study was to investigate the association of Single Nucleotide Polymorphisms of TP53, BRCA1and BRCA2 genes with the susceptibility to PCOS in South Indian women.
Present study investigated association between TP53 gene (rs1042522 G/C), BRCA1 (rs71361504 -/GTT, rs3092986 T/C) and BRCA2 (rs206118 A/G) and, SNPs and PCOS risk. Genotyping of TSGs was carried out on DNA from PCOS patients (n = 110) and controls (n = 130) of South Indian origin by polymerase chain reaction (PCR) and confirmed by sequencing analysis. The genotype frequency and allele distributions of cases and controls were analyzed using Fisher's exact test. Haplotype frequencies for multiple loci and the standardized disequilibrium coefficient (D') for pair wise linkage disequilibrium (LD) were assessed by Haploview Software.
Significant increase in frequencies ofTP53 (rs1042522 G/C), BRCA1 (rs71361504 -/GTT, rs3092986 T/C) genotypes and alleles in patients compared to controls. In addition, the frequency of the C/T (P = 0.002) and A/C (P = 0.012) haplotype was also significantly elevated in patients. But BRCA2 (rs206118 A/G) did not show significant association with PCOS.
The TP53 and BRCA1 may constitute an inheritable risk factor for PCOS in South Indian women.
多囊卵巢综合征（PCOS）是一种异质性多因素内分泌代谢紊乱疾病。除了高雄激素血症、痤疮、多毛、肥胖、排卵稀少和不孕外，胰岛素抵抗也是PCOS女性的常见特征。肿瘤抑制基因（TSGs）在维持基因组稳定性以及影响多种复制和转录因子活性的调控途径中发挥着重要作用。本研究的主要目的是调查南印度女性中TP53、BRCA1和BRCA2基因的单核苷酸多态性与PCOS易感性之间的关联。
本研究调查了TP53基因（rs1042522 G/C）、BRCA1（rs71361504 -/GTT、rs3092986 T/C）和BRCA2（rs206118 A/G）以及单核苷酸多态性（SNPs）与PCOS风险之间的关联。通过聚合酶链反应（PCR）对来自南印度的PCOS患者（n = 110）和对照（n = 130）的DNA进行肿瘤抑制基因的基因分型，并通过测序分析进行确认。使用Fisher精确检验分析病例组和对照组的基因型频率和等位基因分布。通过Haploview软件评估多个位点的单倍型频率以及成对连锁不平衡（LD）的标准化不平衡系数（D'）。
与对照组相比，患者中TP53（rs1042522 G/C）、BRCA1（rs71361504 -/GTT、rs3092986 T/C）基因型和等位基因的频率显著增加。此外，患者中C/T（P = 0.002）和A/C（P = 0.012）单倍型的频率也显著升高。但BRCA2（rs206118 A/G）与PCOS未显示出显著关联。
TP53和BRCA1可能是南印度女性PCOS的一个可遗传风险因素。
