Genes, Air Pollution Combine to Raise Lupus Risk
British research suggests that genetic and environmental factors work to
By John Gever
Exposure to high levels of common air pollutants significantly increased risk for new-onset systemic lupus erythematosus (SLE), and dramatically more so for people with known genetic risk markers, U.K. Biobank data indicated.
The analysis of 460,000 individuals within the British health database found an increase of 18% to 27 percent in the probability for developing SLE for each of the steps in the quartiles of estimated exposure to particulate matter as well as nitrogen oxides, according Jian Yang, PhD, of China Three Gorges University in Yichang, China, and colleagues.
Furthermore, for those categorized as high risk genetically and who had elevated levels of four major pollutants -PM2.5 and PM10 – PM2.5 as well as PM10 (particulate matter 2.5 millimeters or less as well as 10 millimeters or less respectively) and NO2 (NO2) as well as any Nitrogen oxides (NOx) (NOx) — the increase in SLE risk varied from 316% to 461% compared to people with a low environmental exposure and genetic risk The study was published by researchers in Arthritis and Rheumatologyopens in the new tab or open in a new window.
The huge increases were caused predominantly through genetic risks. The people who were high on this risk factor were still at risk of quadrupling risk of developing lupus, even with minimal exposure to particulates or nitrogen oxides. On the other hand the risk increase of around 30% to 70% were estimated for those with lower genetic risk and higher pollution exposures. The results were either not statistically significant or even borderline.
The range of confidence intervals was rather wide, as from the 460,000 patients only 399 were diagnosed with SLE in an average of 11.8 year of following-up.
Therefore, Yang and colleagues were appropriately cautious when they interpreted the results. “Additional cohort studies are needed to elucidate the relationship between specific air pollutants and the development of SLE,” they wrote.
“In addition, the underlying biologic mechanisms linking air pollution exposure to SLE pathogenesis need to be further explored. Given that a meaningful correlation analysis result does not imply a causal association, more studies are needed in the future to confirm the causal link between air pollution and incident SLE.”
The researchers still believed that their research should be considered seriously. “Our current study provided crucial insights into the environmental factors contributing to autoimmune diseases,” they said. “Findings can inform the development of stricter air quality regulations to mitigate exposure to harmful pollutants, thereby reducing the risk of SLE.”
Their findings complement an array of studies which has found environmental factors, like air pollution as a cause of SLE. However, Yang and co-workers noted that the majority of their research relied on exposure information and results like disease activity or hospitalizations, and not on new-onset Lupus. Research on this condition has been conducted however just in Taiwan. “It is essential to evaluate this association in Europe, where the air pollution level is significantly lower,” the authors of the study said.
Yang’s group was inspired by the U.K. Biobankopens in an entirely new tab or window it is a possible project that gathers health records for millions of people in Britain and which was enrolled between 2006 and 2010. It also conducts periodic physical examinations and questionnaires. The samples of tissue are taken to enable genetic analysis.
One-year average exposures to all four pollutants were calculated for the year 2010 based on monitoring information from several years before that time. This was the base of the research team’s statistical analysis. Biobank people who reside in areas that were not regularly monitored were not included. The concentrations of each pollutant was classified into quarters. Medians for each pollutant were as the following:
- PM2.5: 9.93 mg/m3
- PM10: 19.16 mg/m3
- NO2: 28.11 mg/m3
- NOx: 42.26 mg/m3
Risk scores for polygenics were determined for all participants and were then classified into tertiles which define moderate, low and high risks for SLE from earlier study of genome-wide associations.
Statistics were adjusted to take into account many possible covariates such as race/ethnicity, sex, age and income, as well as employment and smoking status and the body mass index.
The mean age of participants at baseline was around 57 (a potential limitation considering that SLE usually begins at the age of young adulthood) Just over half of them were women and more than 90% were white.
Yang and coworkers also looked at the exposure to pollution as a constant variable which revealed that the correlation of pollution exposure with SLE risk was not linear in two out of four pollutant. The NO x and PM 2.5 and NO x displayed the effect of a plateau, and significant correlations with SLE risk in the low to medium exposures, but with no any further increases when exposures increased. Linear associations were observed in NO 2 and PM 10, in addition to NO 2 On contrary.
The study’s limitations, apart from the limited amount of reported SLE cases, and mostly a middle-aged sample, include individuals’ choice to join the Biobank (meaning they could be more conscious about their health than other) as well as the possibility for exposure to pollutants by individuals to be more varied than what was reflected in estimations of annual exposure. Additionally, a variety of possible confounding factors like exposure to other pollutants, such as silica dust or ground-level ozone are not considered.
Disclosures
Yang and co-authors stated that they did not have any financial interest.
Primary Source
Arthritis & Rheumatology
Source Reference opens in a open tabXing M, and others “Air pollution, genetic susceptibility, and risk of incident systemic lupus erythematosus: a prospective cohort study” Arthritis Rheumatol 2024; DOI 10.1002/art.42929.