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Common genetic polymorphisms in manganese transporters SLC30A10, SLC39A8 and SLC39A14, manganese concentrations and neurological function

Palaniselvam, Aberame (2017) MOBT01 20162
Degree Projects in Molecular Biology
Popular Abstract
Genetics for Manganese

Manganese (Mn) is one of the essential minerals for humans and it is mainly present in blood, liver, intestine, and brain. However, at elevated concentrations, for example from occupational or environmental exposure, Mn may be toxic to the nervous system. Despite that Mn concentrations are tightly regulated in the body, concentrations seem to depend on our genetics. The aim of my research was to evaluate how variations in human genetics can affect the concentration of Mn in humans.
Mn is commonly present in human diet. Nuts, cereals, legumes, fruits, vegetables and tea are some of the major dietary sources of Mn. Apart from these; our body gets Mn from drinking water, air and soil. Every day average adult Mn... (More)
Genetics for Manganese

Manganese (Mn) is one of the essential minerals for humans and it is mainly present in blood, liver, intestine, and brain. However, at elevated concentrations, for example from occupational or environmental exposure, Mn may be toxic to the nervous system. Despite that Mn concentrations are tightly regulated in the body, concentrations seem to depend on our genetics. The aim of my research was to evaluate how variations in human genetics can affect the concentration of Mn in humans.
Mn is commonly present in human diet. Nuts, cereals, legumes, fruits, vegetables and tea are some of the major dietary sources of Mn. Apart from these; our body gets Mn from drinking water, air and soil. Every day average adult Mn consumption ranges from 0.7 to 10.9 mg. Mn is readily absorbed in the small intestine or in the lung from inhalation and excess Mn is excreted in feces via the bile. Mn is circulated in blood for its use in different parts of our body. Excess of Mn in blood may cross the blood-brain-barrier and then enters the brain, accumulating mainly in the mid-brain. Excess Mn in the mid brain may results in a condition called manganism, similar to Parkinson’s disease. Manganism is observed in workers, e.g. welders, chronically exposed to high Mn concentrations.
In children, environmental Mn exposure at lower concentrations has in some studies shown adverse effect on childrens' cognitive function such as poor in language skills and mathematics. In order to understand the neurotoxic mechanisms of Mn, we investigated the role of Mn transporter genes on Mn concentrations in different tissues (blood and mid-brain). Is there any specific variation in genes of proteins involved in Mn transport that influence the Mn concentrations and in turn Mn toxicity?

Mn transporter proteins and common genetic variations:
Mn - a divalent cation - is transported by divalent metal protein, ferroportin and solute carrier proteins. Among them, we were interested in the solute carrier protein family proteins SLC30A10, SLC39A8 and SLC39A14 that recently have been linked to Mn toxicity in rare genetic syndromes. The most common type of genetic variation is Single Nucleotide Polymorphism (SNP). We looked at SNPs in these genes and analysed if there was any association between gentoype and Mn concentrations in mid-brain. Secondly, we evaluated SNPs versus blood Mn concentration and neurobehavioral response in children, environmentally exposed to Mn.
There were no significant associations between the SLC30A10, SLC39A8 and SLC39A14 SNPs and Mn concentrations in mid-brain, likely due to low number of samples and thus low statistical power. In the second study, though none of the SNPs showed significant association with neurobehavioral problems and blood Mn concentrations, one SNP labelled in SLC39A14 have more potential to be studied in large population. In future research, further SNPs in SLC39A14 can be selected from genome wide association study to establish their association with circulating Mn levels in humans. More stringent statistical analysis with large number of data might show some significant results. Evaluating the relation between genetic variations in genes encoding the key transport proteins and Mn level in biological system will provide insight on mechanism of Mn transport in humans.

Master’s Degree Project in Biology/Molecular Biology/Bioinformatics 60 credits 2017
Department of Biology, Lund University

Advisor: Karin Broberg
Occupational and Environmental Medicine, Lund University (Less)
Please use this url to cite or link to this publication:
author
Palaniselvam, Aberame
supervisor
organization
course
MOBT01 20162
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
8926557
date added to LUP
2017-09-29 11:38:02
date last changed
2017-09-29 11:38:02
@misc{8926557,
  author       = {Palaniselvam, Aberame},
  language     = {eng},
  note         = {Student Paper},
  title        = {Common genetic polymorphisms in manganese transporters SLC30A10, SLC39A8 and SLC39A14, manganese concentrations and neurological function},
  year         = {2017},
}