Specific Mutations in LTA Gene Determine Risk of Ankylosing Spondylitis, Study Suggests

Specific Mutations in LTA Gene Determine Risk of Ankylosing Spondylitis, Study Suggests
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Variations in the LTA gene can alter a person’s risk of developing ankylosing spondylitis (AS), a new study suggests.

The study, “Associations of lymphotoxin-a (LTA) rs909253 A/G gene polymorphism, plasma level and risk of ankylosing spondylitis in a Chinese Han population,” was published in the journal Scientific Reports.

The LTA gene contains information to make the protein lymphotoxin-a (also known as tumor necrosis factor-beta), which has pro-inflammatory properties. As such, variations (or mutations) in LTA could impact an individual’s risk of developing an immune-related disease like AS.

Researchers in China investigated the relationship between a change in this gene, known as rs909253 A/G, and AS risk. In essence, this variant means that adenine (A) is replaced by guanine (G) at a specific spot in the gene. Because each person has two copies of the gene — one from each parent — someone’s genetic profile in rs909253 may be AA, AG, or GG. (Adenine and guanine are two of four nucleotides, the building blocks of DNA.)

The researchers conducted a genetic analysis of 190 Chinese patients of Han ethnicity with ankylosing spondylitis (142 men, 48 women, average age 32.5), who were treated at one of two hospitals between September 2010 and January 2016. For comparison, they also assessed 190 people without AS (control group). Statistical models were then constructed to compare the relative risk of AS based on genetic profile (called a genotype).

People with the GG genotype (both copies with the G nucleotide) were less likely — nearly by half — to have AS than those with the other two genetic profiles. No significant difference in AS risk was found between the AG and AA profiles.

More broadly, having a gene copy with G was associated with a 30% decrease in AS risk. Further analysis revealed this effect to be specifically significant among people who were younger, women, or positive for HLA-B27 — a protein found on the surface of white blood cells and previously linked to genetic susceptibility for AS.

“In conclusion, LTA rs909253 A/G genotype has a significant relationship with decreased susceptibility to AS,” the scientists wrote.

People with AS had significantly lower levels of the LTA protein in their blood than those without this disorder. However, the different rs909253 genotypes were not associated to variations in LTA levels.

Differences in blood levels of LTA also did not correlate with sex, age, testing positive for HLA-B27 or C-reactive protein (a marker of inflammation), or the severity of damage in the sacroiliac joints in AS patients.

The team then combined their data with those from previous studies that also reported an association between rs909253 and AS risk. Yet, this analysis found no significant correlation between this gene variant and likelihood of having AS.

More research will be needed to clarify these findings, and reveal to the biological processes that may link the mutation with AS.

Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.
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José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.
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Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.
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