Linkage and association of variants in the dopamine receptor 2 gene (DRD2) with polycystic ovary syndrome

Amin, Mutaz; Horst, N; Gragnoli, Claudia

doi:10.1186/s13048-023-01205-2

Cited by 5 publications

(3 citation statements)

References 47 publications

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“…Meanwhile, recent researchers detected 22 corticotropin-releasing hormone receptor (CRHR) CRHR1 variants and 1 CRHR2 variant significantly associated with PCOS ( P < 0.05) in different genetic models [ 29 ]. Five new variants in the dopamine receptor 2 (DRD2) gene that are significantly associated with PCOS risk were also recently identified [ 30 ]. Not only that, but CRHR and DRD2 gene variants are likewise correlated with the development of diabetes mellitus [ 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…Five new variants in the dopamine receptor 2 (DRD2) gene that are significantly associated with PCOS risk were also recently identified [ 30 ]. Not only that, but CRHR and DRD2 gene variants are likewise correlated with the development of diabetes mellitus [ 29 , 30 ]. Therefore, it would be interesting to explore whether there is a correlation or causal relationship between T1D and PCOS in terms of genetic markers.…”

Section: Discussionmentioning

confidence: 99%

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Genetic evidence for the causal association between type 1 diabetes and the risk of polycystic ovary syndrome

Chen,

Guo,

2023

Hum Genomics

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Background Accumulating observational studies have identified associations between type 1 diabetes (T1D) and polycystic ovary syndrome (PCOS). Still, the evidence about the causal effect of this association is uncertain. Methods We performed a two-sample Mendelian randomization (MR) analysis to test for the causal association between T1D and PCOS using data from a large-scale biopsy-confirmed genome-wide association study (GWAS) in European ancestries. We innovatively divided T1D into nine subgroups to be analyzed separately, including: type1 diabetes wide definition, type1 diabetes early onset, type 1 diabetes with coma, type 1 diabetes with ketoacidosis, type 1 diabetes with neurological complications, type 1 diabetes with ophthalmic complications, type 1 diabetes with peripheral circulatory complications, type 1 diabetes with renal complications, and type 1 diabetes with other specified/multiple/unspecified complications. GWAS data for PCOS were obtained from a large-scale GWAS (10,074 cases and 103,164 controls) for primary analysis and the IEU consortium for replication and meta-analysis. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. Results Following rigorous instrument selection steps, the number of SNPs finally used for T1D nine subgroups varying from 6 to 36 was retained in MR estimation. However, we did not observe evidence of causal association between type 1 diabetes nine subgroups and PCOS using the IVW analysis, MR-Egger regression, and weighted median approaches, and all P values were > 0.05 with ORs near 1. Subsequent replicates and meta-analyses also yielded consistent results. A number of sensitivity analyses also did not reveal heterogeneity and pleiotropy, including Cochran’s Q test, MR-Egger intercept test, MR-PRESSO global test, leave-one-out analysis, and funnel plot analysis. Conclusion This is the first MR study to investigate the causal relationship between type 1 diabetes and PCOS. Our findings failed to find substantial causal effect of type 1 diabetes on risk of PCOS. Further randomized controlled studies and MR studies are necessary.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Genetic evidence for the causal association between type 1 diabetes and the risk of polycystic ovary syndrome

Chen,

Guo,

2023

Hum Genomics

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“…Women diagnosed with PCOS reportedly have higher gonadotropin-releasing hormone (GnRH)/LH pulse frequency, which might account for increased PRL levels [64,79]. It has been hypothesized that the irregular secretion of gonadotropins in PCOS could stem from disruptions within the underlying neuroendocrine process that governs the release of GnRH [80]. Persistently high GnRH pulse frequency favors LH production over FSH production.…”

Section: Serum Prolactin Levels In Pcos Women Compared To Healthy Con...mentioning

confidence: 99%

Prolactin in Polycystic Ovary Syndrome: Metabolic Effects and Therapeutic Prospects

Mastnak,

Herman,

Ferjan

et al. 2023

Life

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Polycystic ovary syndrome (PCOS) is the most prevalent endocrine and metabolic disorder in premenopausal women, characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. Patients frequently present comorbidities, including obesity, insulin resistance, and impaired glucose and lipid metabolism. The diverse clinical presentation may mimic various endocrine disorders, making the diagnosis challenging in some clinical circumstances. Prolactin (PRL) is a recommended biomarker in the initial diagnostic workup to rule out hyperprolactinemia (HPRL). The traditional role of PRL is linked to lactation and the reproductive system. Recent research highlights PRL’s emerging role in metabolic homeostasis. PRL influences metabolism directly by interacting with the pancreas, liver, hypothalamus, and adipose tissue. Its influence on an individual’s metabolism is intricately tied to its serum concentration. While deficient and very high levels of PRL can negatively affect metabolism, intermediate–normal to moderately high levels may promote metabolic health. In women with PCOS, PRL levels may be altered. Research results on different aspects of the relationship between PCOS and the impact of various levels of PRL on metabolic homeostasis are limited and inconsistent. In this narrative literature review, we comprehensively examined data on serum PRL levels in PCOS patients. We investigated the correlation between a favorable metabolic profile and serum PRL levels in this population. Furthermore, we explored the concept of beneficial PRL effects on metabolism and discussed the potential therapeutic application of dopamine agonists in PCOS treatment. Lastly, we emphasized several promising avenues for future research in this field.

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What do we know about abnormally low prolactin levels in polycystic ovary syndrome? A narrative review

Cera,

Pinto,

Pignatelli

2024

Rev Endocr Metab Disord

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Hyper and hypoprolactinemia seem to be related to the occurrence of metabolic alterations in PCOS patients. In contrast, between significantly elevated and significantly low, prolactin levels seem to be protective against metabolic consequences. In the present review, we found 4 studies investigating hypoprolactinemia in patients with PCOS. We also identified 6 additional studies that reported low levels of PRL in PCOS patients. Although its prevalence is not considered high (13.2–13.9%), its contribution is certainly significant to the metabolic alterations observed in PCOS (insulin resistance, obesity, diabetes mellitus, and fatty liver disease). Dopamine inhibits the secretion of prolactin and GnRH. If dopamine levels are low or the dopamine receptor is less expressed or mutated, the levels of prolactin and GnRH increase, and consequently, LH also increases. On the other hand, hyperprolactinemia, in prolactinomas-typical levels, acting through kisspeptin inhibition causes GnRH suppression and hypogonadotropic hypogonadism. In situations of hypoprolactinemia due to excessive dopamine agonist treatment, dosage reduction is important to minimize the decrease in prolactin levels. Nevertheless, there is a lack of prospective studies confirming these hypotheses, as well as randomized clinical trials with appropriate drugs targeting both hyperprolactin and hypoprolactin in patients with PCOS.

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Linkage and association of variants in the dopamine receptor 2 gene (DRD2) with polycystic ovary syndrome

Cited by 5 publications

References 47 publications

Genetic evidence for the causal association between type 1 diabetes and the risk of polycystic ovary syndrome

Genetic evidence for the causal association between type 1 diabetes and the risk of polycystic ovary syndrome

Prolactin in Polycystic Ovary Syndrome: Metabolic Effects and Therapeutic Prospects

What do we know about abnormally low prolactin levels in polycystic ovary syndrome? A narrative review

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