Associations between IL12B Polymorphisms and Tuberculosis in the Hong Kong Chinese Population

Background. Interleukin (IL)-12 plays a vital role in regulating cell-mediated immunity against tuberculosis (TB). Methods. To test whether IL12B genetic polymorphisms might contribute to human TB susceptibility, we examined the genotype frequencies of 5 IL12B polymorphisms (at promoter, intron 2, intron 4, exon 5, and 3′ untranslated region [UTR]) in 516 patients with TB and 514 healthy control subjects from the Hong Kong Chinese population. Results. Individuals homozygous for the IL12B intron 2-repeat marker (ATT)8 had a 2.1-fold increased risk of developing TB (P < .001) (odds ratio, 2.14 [95% confidence interval, 1.45–3.19]). Estimation of the frequencies of multiple-locus haplotypes composed of IL12B promoter, intron 2, intron 4, and 3′ UTR alleles revealed potential risk haplotypes (designated “A” and “K”) and protective haplotypes (designated “B”) for TB. Furthermore, combining the genotype data of the 4 informative IL12B loci revealed a strong association between a specific genotype pattern, termed “diplotype I” (heterozygous A and K haplotypes), and TB. In contrast, diplotype II (homozygous BB haplotypes) appeared protective against TB. Conclusions. These findings support the association between IL12B intron 2 polymorphism and TB and between specific IL12B haplotypes and TB.