Tuberculosis resistance

Two loci control tuberculin skin test reactivity in an area hyperendemic for tuberculosis:

Approximately 20% of persons living in areas hyperendemic for tuberculosis (TB) display persistent lack of tuberculin skin test (TST) reactivity and appear to be naturally resistant to infection by Mycobacterium tuberculosis. Among those with a positive response, the intensity of TST reactivity varies greatly. The genetic basis of TST reactivity is not known. We report on a genome-wide linkage search for loci that have an impact on TST reactivity, which is defined either as zero versus nonzero (TST-BINa) or as extent of TST in millimeters (TST-quantitative trait locus [QTL]) in a panel of 128 families, including 350 siblings, from an area of South Africa hyperendemic for TB. We detected a major locus (TST1) on chromosomal region 11p14 (P = 1.4 x 10-5), which controls TST-BINa, with a lack of responsiveness indicating T cell-independent resistance to M. tuberculosis. We also detected a second major locus (TST2) on chromosomal region 5p15 (P Fine mapping of this region identified SLC6A3, encoding the dopamine transporter DAT1, as a promising gene for further studies. Our results pave the way for the understanding of the molecular mechanisms involved in resistance to M. tuberculosis infection in endemic areas (TST1) and for the identification of critical regulators of T cell-dependent DTH to tuberculin (TST2).

They focus on rs250682 in particular. It seems to me that personal genomics in the interests of health has been a little over-hyped, but I will be happy when people with allergies can get their genes sequenced rather than taking these irritating skin tests.

Citation: Aurelie Cobat, Caroline J. Gallant, Leah Simkin, Gillian F. Black, Kim Stanley, Jane Hughes, T. Mark Doherty, Willem A. Hanekom, Brian Eley, Jean-Philippe Jaïs, Anne Boland-Auge, Paul van Helden, Jean-Laurent Casanova, Laurent Abel, Eileen G. Hoal, Erwin Schurr, and Alexandre Alcaïs, Two loci control tuberculin skin test reactivity in an area hyperendemic for tuberculosis, J. Exp. Med., Nov 2009; 206: 2583 - 2591.

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I'm skeptical of how well those skin-prick allergy tests work. I typically react to almost everything, which makes no sense at all. (I was trying to eliminate my cat allergy for a girl, at the time. Now I just date women with dogs.)

I also think a fair # of allergy treatment patients don't want more accurate results. It's a fairly low-cost hypochondriac activity. They enjoy having and discussing allergies. Look at the huge # of Americans who claim to have a food allergy, but who objectively don't. And if a doctor tells them they don't have a real allergy, they just change doctors. Or start going to some quack natural herbologist, and not mention their allergy "treatments" to their real doctor.

Don't get me wrong, it would be good if a simple blood test could accurately detect real allergies. I just think the current lack of accuracy in allergy diagnosis, for many patients, is a feature. not a bug.

Razib,

23AndMe don't test for this SNP, but do test for a different SNP linked to Tuberculosis resistance:
rs4804803

I have the GG variant, meaning slightly lower odds of getting TB.

Here's what they say:
This study compared 1,262 tuberculosis patients from four African countries to 914 healthy controls and found that those with the GG genotype at rs4804803 had 0.86 times the odds of being susceptible to tuberculosis compared to individuals with one A and one G. Those with the AA genotype at rs4804803 had 1.16 times the odds. The researchers also found that people with the GG genotype who did develop the disease were less likely to develop cavitory tuberculosis, a severe form of the infection.