Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0003128 (anovulation)
 1,718 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polycystic ovary syndrome (PCOS) is a common endocrine disorder of women, characterized by hyperandrogenism and chronic anovulation. It is a leading cause of female infertility and is associated with polycystic ovaries, hirsutism, obesity, and insulin resistance. We tested a carefully chosen collection of 37 candidate genes for linkage and association with PCOS or hyperandrogenemia in data from 150 families. The strongest evidence for linkage was with the follistatin gene, for which affected sisters showed increased identity by descent (72%; chi(2) = 12.97; nominal P = 3.2 x 10(-4)). After correction for multiple testing (33 tests), the follistatin findings were still highly significant (P(c) = 0.01). Although the linkage results for CYP11A were also nominally significant (P = 0.02), they were no longer significant after correction. In 11 candidate gene regions, at least one allele showed nominally significant evidence for population association with PCOS in the transmission/disequilibrium test (chi(2) >/= 3.84; nominal P < 0.05). The strongest effect in the transmission/disequilibrium test was observed in the INSR region (D19S884; allele 5; chi(2) = 8.53) but was not significant after correction. Our study shows how a systematic screen of candidate genes can provide strong evidence for genetic linkage in complex diseases and can identify those genes that should have high (or low) priority for further study.
 ...
PMID:Thirty-seven candidate genes for polycystic ovary syndrome: strongest evidence for linkage is with follistatin. 1041 66

The polycystic ovary syndrome (PCOS) is one of the commonest female endocrinopathies affecting 5-10% of women of reproductive age. The disorder, characterized by chronic anovulation and signs of hyperandrogenism, results from a complex interaction between genetic predisposing factors and environmental triggers. We have studied 85 Caucasian PCOS patients and 87 age-matched Caucasian control women for associations with four candidate genes: follistatin, CYP19 (aromatase), CYP17a, and the insulin receptor (INSR). These genes were analyzed using microsatellite markers located near or inside the genes. We found that only the insulin receptor gene marker D19S884 was significantly associated with PCOS (p=0.006 and even after a conservative correction p=0.042). The INSR gene region was then fine mapped with an additional panel of 9 markers but only marker D19S884, located 1 cM telomeric to the INSR gene, was again associated with PCOS. In conclusion, our results suggested that a susceptibility gene for PCOS was located on chromosome 19p13.3 in the insulin receptor gene region. It remains to be determined if this susceptibility gene is the insulin receptor gene itself or a closely located gene. Since insulin stimulates androgen secretion by the ovarian stroma it is likely that INSR function in the ovary is involved in the genetic susceptibility ot PCOS.
 ...
PMID:Evidence for association of polycystic ovary syndrome in caucasian women with a marker at the insulin receptor gene locus. 1123 39

The mechanism of the increase in the number of follicles in polycystic ovaries (PCO) is still not understood, but most data indicate that folliculogenesis is abnormal at all stages. This increase is probably due to prolonged follicle growth in both ovulatory (ov) and anovulatory PCO (anovPCO) rather than over-recruitment from the primordial stage. There appear to be fewer follicles in ovPCO than in anovPCO and this may be due to slow growth combined with arrested development in the anovPCO, preventing the normal process of atresia. This idea is supported by data indicating that the preponderance of structures in anovPCO are functional follicles rather than atretic cysts. In contrast, follicles in ovPCO are primarily atretic, analogous to the situation in the normal ovary. Closer analysis of the function of these follicles reveals an intrinsic defect in the theca cell layer in the expression of the genes encoding steroidogenic enzymes. Although androgen production is increased in all PCOs, the serum concentrations of androgen tended to be higher in anovulatory women indicating that there may be a link between the ovarian concentration and anovulation. Granulosa cells in small follicles from anovPCO behave in a similar fashion to those in preovulatory follicles from normal ovaries in terms of steroidogenic responses. This, in combination with the finding of LH-responsiveness in small follicles from anovPCO, has led to the suggestion that these follicles are prematurely luteinized. The recent finding that follistatin gene regulation may be abnormal in women with polycystic ovary syndrome (PCOS) provides a new insight into the possible defect in the function of these ovaries. Elucidation of the precise nature of the defect may provide the key to understanding the apparent contradiction of increased steroidogenesis in the presence of abnormal and arrested follicle growth.
 ...
PMID:Function of the polycystic ovary. 1184 59