Association of functional mutant homozygotes of the mannose binding protein gene with susceptibility to pulmonary tuberculosis in India

Selvaraj, P.; Narayanan, P R; Reetha, A M

doi:10.1054/tuld.1999.0204

Cited by 93 publications

(68 citation statements)

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“…The B allele frequency in the controls of the present study (0·11) is similar to that reported earlier for Indian control individuals (0·11) and comparable to that reported for Caucasians, Chinese and Eskimos (0·11-0·17) [33,34]. The frequency of the D allele in our study (0·01) is also comparable with the earlier frequency reported in Indian individuals (0·04) and to that of Caucasians (0·05) and Africans (0·05) [33][34][35][36]. Also, the frequency of the C allele in the present study (0·08) is comparable to that reported earlier in Indian individuals (0·03) and also to Caucasians (0·02), but lower than in Africans (0·23-0·29) [35].…”

Section: Discussionsupporting

confidence: 81%

“…A recent study on animal models of Afuinduced asthma by Hogaboam et al [32] showed that in Afusensitized murine MBL-A-deficient mice whole lung T helper cell type 2 cytokine levels were decreased significantly, and whole lung interferon-gamma levels were increased significantly when compared with normal mice, indicating that the murine MBL-A contributes to the development and maintenance of airway hyperresponsiveness. As well as the novel intronic SNP, the three exon 1 SNPs [G875A (B allele), G884A (C allele) and C868T (D allele)] at codons 54, 57 and 52, respectively, leading to low plasma MBL levels that have been reported in other populations including the Indian population, were also present in our study population [13,[33][34][35][36]. The B allele frequency in the controls of the present study (0·11) is similar to that reported earlier for Indian control individuals (0·11) and comparable to that reported for Caucasians, Chinese and Eskimos (0·11-0·17) [33,34].…”

Section: Discussionmentioning

confidence: 59%

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Elevated levels of mannan-binding leptin (MBL) and eosinophilia in patients of bronchial asthma with allergic rhinitis and allergic bronchopulmonary aspergillosis associate with a novel intronic polymorphism in MBL

Kaur

Gupta

Shah

et al. 2006

Clinical and Experimental Immunology

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SummaryMannan-binding lectin (MBL), an important component of innate immunity, binds to a range of foreign antigens and initiates the lectin complement pathway. Earlier studies have reported high plasma MBL levels in allergic patients in comparison to healthy controls. In view of varied plasma MBL levels being determined by genetic polymorphisms in its collagen region, we investigated the association of single nucleotide polymorphisms (SNPs) in the collagen region of human MBL with respiratory allergic diseases. The study groups comprised patients of bronchial asthma with allergic rhinitis ( n = = = = 49) and allergic bronchopulmonary aspergillosis (APBA) ( n = = = = 11) and unrelated agematched healthy controls of Indian origin ( n = = = = 84). A novel intronic SNP, G1011A of MBL , showed a significant association with both the patient groups in comparison to the controls ( P < < < < 0·01). Patients homozygous for the 1011A allele showed significantly higher plasma MBL levels and activity than those homozygous for the 1011G allele ( P < < < < 0·05). The 1011A allele also showed a significant correlation with high peripheral blood eosinophilia ( P < < < < 0·05) and low forced expiratory volume in 1 s (FEV 1 ) ( P < < < < 0·05) of the patients. We conclude that the 1011A allele of MBL may contribute to elevated plasma MBL levels and activity and to increased severity of the disease markers in patients of bronchial asthma with allergic rhinitis and ABPA.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 59%

Elevated levels of mannan-binding leptin (MBL) and eosinophilia in patients of bronchial asthma with allergic rhinitis and allergic bronchopulmonary aspergillosis associate with a novel intronic polymorphism in MBL

Kaur

Gupta

Shah

et al. 2006

Clinical and Experimental Immunology

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“…The high incidence of heterozygosity for the structural variants in many populations throughout the world 9,10 suggests that there may be a selective advantage for heterozygotes; moreover, individuals heterozygous for B, C and D may be protected against certain pathogens, especially intracellular microorganisms (ie, Mycobacteria spp and Leishmania spp. [21][22][23][24][25][26][27] The fact that there are only seven common haplotypes (eg, HYPA, HYPD, LXPA, LYPA, LYPB, LYQA and LYQC) further supports the role for recent selective pressure on MBL2. MBL deficiency, measured as low serum levels, has been associated with susceptibility to infection in children and adults.…”

mentioning

confidence: 99%

Sequence analysis of the mannose-binding lectin (MBL2) gene reveals a high degree of heterozygosity with evidence of selection

et al. 2004

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Human mannose-binding protein (MBL) is a component of innate immunity. To capture the common genetic variants of MBL2, we resequenced a 10.0 kb region that includes MBL2 in 102 individuals representing four major US ethnic groups. In all, 87 polymorphic sites were observed, indicating a high level of heterozygosity (total p ¼ 18.3 Â 10 À4 ). Estimates of linkage disequilibrium across MBL2 indicate that it is divided into two blocks, with a probable recombination hot spot in the 3 0 end. Three non-synonymous SNPs in exon 1 of the encoding MBL2 gene and three upstream SNPs form common 'secretor haplotypes' that can predict circulating levels. Common variants have been associated with increased susceptibility to infection and autoimmune diseases. The high frequencies of B, C and D alleles in certain populations suggest a possible selective advantage for heterozygosity. There is limited diversity of haplotype structure; the 'secretor haplotypes' lie on a restricted number of extended haplotypes, which could include additional linked SNPs, which might also have possible functional implications. There is evidence for gene conversion in the region between the two blocks, in the last exon. Our data should form the basis for conducting MBL2 candidate gene association studies using a locus-wide approach. Keywords: mannose-binding lectin; innate immunity; genetic variation; recombination hot spot; gene conversion IntroductionThe human mannose-binding protein (MBL) is an important component of the innate immune system and provides first-line protection against pathogens as an 'ante-antibody'. 1 MBL is a C-type collectin that functions as a pattern-recognition molecule in the immediate response to invading organisms. Carbohydrate structures on the surfaces of microorganisms (bacteria, fungi and parasites) are recognized by MBL, 2-5 which, in turn, lead to opsonization or activation of the lectin pathway of complement via associated mannosebinding lectin serine proteases (MASP2). [6][7][8] Decreased serum levels of MBL have been correlated with an increased risk for infection in both healthy children and immunocompromised individuals. Circulating levels of MBL and functional activity are partially regulated by genetic variation in the MBL2 gene, which encodes MBL. 9,10 The MBL2 gene is located on chromosome 10q11.2-21 and consists of four exons. 11 Each of the three structural gene polymorphisms in exon 1, known as the B, C and D alleles, interfere with the formation of higher MBL oligomers, leading to alterations in function and circulating levels. [12][13][14][15] Two strongly linked single-nucleotide polymorphisms (SNPs) lie in the proximal promoter (known as L/H and X/Y), as well as an SNP in the 5 0 UTR (known as P/Q); together, these upstream SNPs are linked to the three independent nonsynonymous SNPs (ie, B, C and D) to form the 'secretor haplotypes', which have previously been shown to partially account for alterations in complement activation and decreased circulating levels of MBL. 7,9,10,[16][17][18][19][20] Using ...

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“…167 However, no associations have been reported between leprosy susceptibility and MBL2 variants, and in contradiction to the above reports, MBL2 variants were found with increased frequency in a limited Indian pulmonary tuberculosis study. 168 …”

mentioning

confidence: 99%

Genetics of susceptibility to leprosy

2002

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The ancient disease of leprosy can cause severe disability and disfigurement and is still a major health concern in many parts of the world. Only a subset of those individuals exposed to the pathogen will go on to develop clinical disease and there is a broad clinical spectrum amongst leprosy sufferers. The outcome of infection is in part due to host genes that influence control of the initial infection and the host's immune response to that infection. Identification of the host genes that influence host susceptibility/resistance will enable a greater understanding of disease pathogenesis. In turn, this should facilitate development of more effective therapeutics and vaccines. So far at least a dozen genes have been implicated in leprosy susceptibility and a genome-wide linkage study has lead to the identification of at least one positional candidate. These findings are reviewed here.

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Association of functional mutant homozygotes of the mannose binding protein gene with susceptibility to pulmonary tuberculosis in India

Cited by 93 publications

References 26 publications

Elevated levels of mannan-binding leptin (MBL) and eosinophilia in patients of bronchial asthma with allergic rhinitis and allergic bronchopulmonary aspergillosis associate with a novel intronic polymorphism in MBL

Elevated levels of mannan-binding leptin (MBL) and eosinophilia in patients of bronchial asthma with allergic rhinitis and allergic bronchopulmonary aspergillosis associate with a novel intronic polymorphism in MBL

Sequence analysis of the mannose-binding lectin (MBL2) gene reveals a high degree of heterozygosity with evidence of selection

Genetics of susceptibility to leprosy

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