Please use this identifier to cite or link to this item: https://www.um.edu.mt/library/oar/handle/123456789/119126
Title: High population frequency of GNRHR p. Q106R in Malta : an evaluation of fertility and hormone profiles in heterozygotes
Authors: Axiak, Clayton John
Pleven, Adrian
Attard, Ritienne
Borg Carbott, Francesca
Ebejer, Jean Paul
Brincat, Ian
Cassar, Karen
Gruppetta, Mark
Vassallo, Josanne
Bezzina Wettinger, Stephanie
Farrugia, Rosienne
Keywords: Hypogonadism
Receptors, LHRH
Hypogonadism -- Malta
Infertility -- Malta
Kallmann Syndrome
Issue Date: 2024
Publisher: Oxford University Press
Citation: Axiak, C. J., Pleven, A., Attard, R., Borg Carbott, F., Ebejer, J. P., Brincat, I.,...Farrugia, R. (2024). High Population Frequency of GNRHR p. Q106R in Malta: An Evaluation of Fertility and Hormone Profiles in Heterozygotes. Journal of the Endocrine Society, 8, 1-13.
Abstract: Context: The gonadotropin-releasing hormone receptor variant GNRHR p.Q106R (rs104893836) in homozygosity, compound heterozygosity, or single heterozygosity is often reported as the causative variant in idiopathic hypogonadotropic hypogonadism (IHH) patients with GnRH deficiency. Genotyping of a Maltese newborn cord-blood collection yielded a minor allele frequency (MAF) 10 times higher (MAF = 0.029; n = 493) than that of the global population (MAF = 0.003). Objective: To determine whether GNRHR p.Q106R in heterozygosity influences profiles of endogenous hormones belonging to the hypothalamic-pituitary axis and the onset of puberty and fertility in adult men (n = 739) and women (n = 239). Design, Setting, and Participants: Analysis of questionnaire data relating to puberty and fertility, genotyping of the GNRHR p.Q106R variant, and hormone profiling of a highly phenotyped Maltese adult cohort from the Maltese Acute Myocardial Infarction Study. Main Outcome and Results: Out of 978 adults, 43 GNRHR p.Q106R heterozygotes (26 men and 17 women) were identified. Hormone levels and fertility for all heterozygotes are within normal parameters except for TSH, which was lower in men 50 years or older. Conclusion: Hormone data and baseline fertility characteristics of GNRHR p.Q106R heterozygotes are comparable to those of homozygous wild-type individuals who have no reproductive problems. The heterozygous genotype alone does not impair the levels of investigated gonadotropins and sex steroid hormones or affect fertility. GNRHR p.Q106R heterozygotes who exhibit IHH characteristics must have at least another variant, probably in a different IHH gene, that drives pathogenicity. We also conclude that GNRHR p.Q106R is likely a founder variant due to its overrepresentation and prevalence in the island population of Malta.
URI: https://www.um.edu.mt/library/oar/handle/123456789/119126
Appears in Collections:Scholarly Works - FacM&SMed



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