People of Indigenous descent in Canada seem to have the highest prevalence of spinal and bulbar muscular atrophy (SBMA) of any populations in the world, according to a new study.
Compared to an SBMA prevalence of one to two per 100,000 in the general population, it’s 14.7 per 100,000 people in the Indigenous population.
The study, “Highly Elevated Prevalence of Spinobulbar Muscular Atrophy in Indigenous Communities in Canada Due to a Founder Effect,” was published in the journal Neurology Genetics.
SBMA, also known as Kennedy’s disease, is a rare, hereditary adult-onset form of spinal muscular atrophy that is marked by widespread muscle weakness and wasting in the arms, legs, head, and neck (bulbar involvement).
The disorder is caused by mutations that lead to an abnormal expansion of a CAG nucleotide (the building blocks of DNA) in the androgen receptor (AR) gene, located on the X chromosome. As a consequence, the disease mostly affects men.
Previous studies have estimated that SBMA prevalence ranged from one to two persons per 100,000. However, several observations suggested that its prevalence might be higher among individuals of Indigenous descent in Canada, possibly due to a genetic founder effect — a loss of genetic variation that can occur in small populations.
This means that if a particular mutation is present in a small population, it can become prevalent as this population grows and shares a common ancestor.
In this study, researchers at the University of Saskatchewan (USask) and University of Calgary investigated the prevalence of SBMA among the Prairie provinces of Canada, specifically in the province of Saskatchewan.
“Several of us who have practices in neuromuscular disease in the Prairie provinces and Ontario have suspected that there is a much higher prevalence in our Indigenous population,” Kerri Schellenberg, MD, associate professor of neurology at USask, medical director of the ALS Clinic at Saskatoon’s City Hospital, and the study’s co-lead author said in a university press release.
The researchers analyzed data from patients with SBMA in the Saskatoon neuromuscular clinic database. They also contacted other neurologists and physiatrists in Saskatchewan who followed patients with neuromuscular disease.
Out of 29 patients with SBMA followed at the Saskatoon clinic, 26 of them had declared themselves of Indigenous ancestry.
Most of them identified as Cree and Saulteaux, but not all of those identified as Indigenous were able to identify their ancestral nations.
Results revealed that the prevalence of SBMA was several fold higher among those of Indigenous descent in Saskatchewan — 14.7 per 100,000 persons — compared to the prevalence in the general Canadian population.
“Although we believe that this is an underestimate, this still appears to be the highest population prevalence for SBMA in the world,” the researchers wrote.
Schellenberg, in collaboration with neurologist Gerald Pfeffer, MD, at the University of Calgary, conducted a genetic analysis to identify a potential founder haplotype — a set of DNA variations, or polymorphisms, that tend to be inherited together — that could explain the high prevalence.
DNA from 21 patients were used in the haplotype analysis. The results revealed that 13 of the patients, all of Indigenous ancestry, clearly shared a haplotype. Four other participants, who did not report Indigenous ancestry, shared a small portion of this same haplotype, “but it is possible that this could have occurred by chance,” the researchers wrote.
Further analysis revealed that the haplotype shared by most of the patients of Indigenous ancestry had originated 10 generations ago, which corresponds to 250 years.
Following the discovery of such a high prevalence of SBMA among those with Indigenous ancestry, Schellenberg and Pfeffer reached out to Alexandra King, MD, and Malcolm King, PhD, “two Indigenous faculty members of USask’s College of Medicine who head pewaseskwan Indigenous Wellness Research Group,” according to the press release.
With the help of the Kings and support from pewaseskwan staff, they invited all participants of the study to an online meeting where they presented their findings and welcomed feedback.
“Before we presented the information to anybody else, we had a meeting with the participants of that research study,” Schellenberg said. “We presented it and then we sat down and listened. It became clear that this was of strong interest to people, and they wanted to see the project move forward.”
According to the participants, the findings highlight the need for future research to better understand the high SBMA prevalence in their communities, as well as the need to increase awareness of SBMA and for additional resources to support those affected.
They also expressed interested in connecting researchers with Indigenous Knowledge Holders, Elders, and local community leaders to discuss the findings.
“There are significant health inequalities between Indigenous and non-Indigenous people in Canada, influenced by a variety of historical and sociopolitical factors,” the researchers wrote.
“This may yet reveal other important genetic discoveries that could have an impact on the diagnosis and care for genetic conditions in Indigenous communities or other underserved populations,” they added.
With a $50,000 grant from the Kennedy’s Disease Association, the researchers will continue their investigation and expand their analysis to Edmonton, Calgary, Winnipeg, Thunder Bay, and Ontario. They will continue also to work with participants from Saskatoon, in close collaboration with the Kings and pewaseskwan.
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