SNPwatch: Genetic Association Study of Leprosy Yields New Insights into an Ancient Disease

Mycobacterium_leprae

Leprosy is a chronic, disabling disease caused by a bacterium (Mycobacterium leprae) that infects only humans and armadillos. The disease affects the skin and peripheral nerves, leading to sores, numbness in the limbs, muscle weakness, and, in severe cases, disfiguring nodules on the skin. Known since biblical times, leprosy was highly stigmatized until the latter part of the 19th century, when the Norwegian doctor Gerhard Hansen discovered that it was caused by a microorganism.

Although multi-drug therapy has cured millions of people of leprosy in recent decades, hundreds of thousands of new cases still occur per year, mostly in developing countries. Finding a way to eradicate the disease is therefore considered important for reducing the number of preventable disabilities worldwide.

Because Mycobacterium leprae is specific to humans and cannot be grown in lab dishes, research into factors influencing disease susceptibility and clinical outcomes has been limited. But the host environment as well as the bacterium itself can affect the course of the disease; in other words, human genetic factors may play an important role in determining who is more susceptible to infection. Since leprosy has been shown to cluster in families, scientists suspect that much of the variability in disease susceptibility and symptoms stems from diversity in individual human immune systems rather than differences between and within strains of the bacteria.

In a new study published today in New England Journal of Medicine, a team of researchers reports new human genetic factors associated with susceptibility to leprosy in Asians. Led by Fu-Ren Zhang of the Shangdong Academy of Medical Sciences in China and Jian-Jun Liu of the Genome Institute of Singapore, the scientists tested 93 variants across an estimated 50 genes in 3254 Chinese individuals with leprosy and 5955 Chinese individuals without the condition. Their analysis identified variants in seven of these genes to be significantly associated with leprosy.

“The discovery of these genes is a major breakthrough for research in leprosy and infectious diseases in general, and will be significant in the early diagnosis and development of new treatments,” said Dr. Liu in a press release.

The strongest of the associations were rs602875 in HLA-DR-DQ, rs3764147 in C13orf31, and rs9302752 in NOD2. In addition, some of the genetic variants were more strongly associated with a form of leprosy that results in more severe symptoms, known as the multibacillary form. These included rs9302752 in NOD2 and the variant rs1491938 in LRRK2.

(23andMe Complete Edition customers can check their data for SNPs reported in this study using the Browse Raw Data feature. See table at the end of this post.)

Altogether, five of the seven genes identified in the study could be shown to interact biologically in the context of immune response to infection. Two of these five genes, NOD2 and TNFSF15, harbor genetic variants that are also associated with Crohn’s disease (see 23andMe’s report on this condition). Crohn’s manifests some common features with leprosy at the cellular level and other researchers have suggested that mycobacterial infection may be a risk factor for Crohn’s. The findings reported by Zhang and Liu and their colleagues provide additional evidence for shared disease mechanisms between Crohn’s disease and leprosy and may increase the range of treatment options for both conditions.

Variants significantly associated with leprosy in individuals of Asian ancestry

SNP Gene/Region Version* Effect (Change in Odds)
rs602875 HLA-DR-DQ G 0.67
rs42490 RIPK2 A 0.76
rs6478108 TNFSF15 T 1.37
rs1873613 LRRK2 C 0.81**
rs3088362 CCDC122 A 1.52
rs3764147 C13orf31 G 1.68
rs9302752 NOD2 C 1.59

* As reported on the 23andMe website through the Browse Raw Data feature.

** Effect only applicable to the multibacillary form of leprosy. LRRK2 is better known as a susceptibility gene for Parkinson’s disease (see 23andMe’s report on this condition). Interestingly, PARK2, another gene linked to Parkinson’s, was associated with leprosy in earlier studies. The reason for the connection between Parkinson’s and leprosy is unclear, though researchers have speculated that some of the same treatments may be effective for both conditions.

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.


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