Title : Whole genome microarray analysis in hyperprolactinemia
Abstract:
Background: Despite the known causes of pituitary adenoma and drug induced, a high percentage of hyperprolactinemia cases remain idiopathic. Further, mechanisms of anti-prolactin autoantibody development in macroprolactinemia cases are not clearly known. Studies at whole genome level will explicate possible genetic contributors to etiopathology of hyperprolactinemia and macroprolactinemia.
Materials and Methods: Whole genome microarray was done DNA High Density Bead Microarray Illumina Infinium Assay (300k bead array) in 27 hyperprolactinemia cases (prolactin >100ng/ml), out of which 8 were macroprolactinemia (4 pituitary adenoma; 4 idiopathic) and 19 were true hyperprolactinemia cases (14 pituitary adenoma; 5 idiopathic). The observed Copy Number Variations (CNVs) were compared with control databases of genomic variants and CNV control database. Further analysis of CNVs specific to the study cases was carried out by online data analysis resources to find out likely pathogenicity.
Results and Discussion: There were 22 CNVs, including both loss and gains; and 31 loss of heterozygosity (LOH) regions found in both idiopathic and pituitary adenoma cases. Gain of HCCS gene in a case of idiopathic hyperprolactinemia with macroprolactinemia and loss of OLFML1 gene in a case of pituitary adenoma with true hyperprolactinemia are suggested to be associated with hyperprolactinemia condition. HCCS has role in mitochondrial respiratory chain and programmed cell death. OLFML1 is involved in cell proliferation. Also, STAT5, which is involved in downstream signal transduction of prolactin, is a regulator of OLFML1. The findings will help to elucidate the biochemical pathways involved and targeted treatment approaches could be developed.
Audience Take Away:
- Studies at whole genome level will explicate possible genetic contributors to etiopathology of hyperprolactinemia and macroprolactinemia.
- Future investigations are required to clearly elucidate the pathogenicity HCCS and OLFML1 in association with hyperprolactinemia.
- Information about genetic predictors associated with the development of hyperprolactinemia condition could lead to the development of targeted treatment approaches.
