Credit: NIGMS
Researchers have identified mutations in microRNAs (miRNAs) that are closely associated with certain global populations and have been implicated in cancers.
The group discovered 31 miRNAs containing variants that occur with different frequencies in African and non-African populations.
Seven of these miRNAs have been linked to the onset, progression, and spread of cancers with known health disparities between patients of European and African descent.
And a variant in one of these miRNAs is associated with a significantly increased risk of non-Hodgkin lymphoma (NHL).
These findings appear in BMC Medical Genomics.
To better understand miRNA diversity across the world, the researchers searched for miRNA variants in the genome sequences of 69 individuals from 14 populations in Europe, Asia, the Americas, and Africa. The samples included genetic material from diverse African populations, including 3 hunter-gatherer populations.
“We wanted to try to see if there was variability in miRNA that hadn’t been identified before,” said study author Renata A. Rawlings-Goss, PhD, of the University of Pennsylvania’s Perelman School of Medicine in Philadelphia.
Overall, the researchers found that miRNA sequences were similar across the populations they sampled. But they did identify 33 novel variants and found that variants in 31 miRNAs were population-differentiated.
The team searched available databases to see which genes these miRNAs were known to inhibit. Their query turned up a large proportion of genes involved in glucose and insulin metabolism, indicating a possible connection between diabetes risk and possessing one of these variants. The search also pointed to effects on genes implicated in cancers.
Specifically, 7 of the population-differentiated miRNAs are currently implicated as cancer biomarkers: hsa-mir-202, hsa-mir-423, hsa-mir-196a-2, hsa-mir-520h, hsa-mir-647, hsa-mir-943, and hsa-mir-1908.
Of particular interest was hsa-mir-202, which contained one of the most highly population-differentiated variants in the dataset and is under investigation as a marker for NHL and early stage breast cancer.
Recent research suggested that a T allele at SNP rs12355840 in hsa-mir-202 helps protect against death from breast cancer by increasing mature hsa-mir-202 expression levels, which leads to downregulation of its gene targets.
On the other hand, diminished expression of mature hsa-mir-202 in subjects harboring at least 1 non-T allele resulted in a significantly elevated risk of NHL (odds ratio=1.83, P=0.008).
Dr Rawlings-Goss and her colleagues found that African/African-American populations had a lower frequency of the T allele compared to European/Asian populations—26% vs 65%, on average. And this suggests decreased baseline expression levels of mature hsa-mir-202 in African populations.
“It’s becoming more and more apparent that miRNAs can have a broad-reaching and global effect on our health and adaptation to disease,” Dr Rawlings-Goss said. “Learning more about differences across populations could be helpful to doing early diagnostics and treating disease across diverse populations.”
