CCR5 32 deletion and atopic asthma in India
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《胸》
Molecular Immunogenetics Laboratory, Institute of Genomics and Integrative Biology, Delhi, India
Correspondence to:
Dr B Ghosh
Molecular Immunogenetics Laboratory, Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India; bghosh@igib.res.in
Keywords: asthma; atopy; CCR5; genetics
Chemokine receptor 5 (CCR5) contributes to the generation of a Th1 immune response by interacting with agonists such as RANTES, MIP-1, and MIP-1?.1 A 32 base pair deletion (32) in CCR5 has been proposed to protect individuals against HIV infection and to bias the immune system towards a Th2-driven response, thus affecting the susceptibility to develop allergic diseases such as asthma. In a study in Scottish children, Hall et al reported an association of CCR532 with a reduced risk of asthma2 but found no such association in adults with asthma.3 In addition, no association was detected with atopy or asthma/wheeze in two other studies.4,5
We examined the potential role for this deletion in the pathogenesis of asthma by an association study in a genetically untapped Indian population. Patients were diagnosed with asthma on the basis of the National Asthma Education and Prevention Program (Expert Panel Report 2) guidelines. Written consent was obtained from individuals participating in the study. Genomic DNA from patients with atopic asthma (mean (SD) age 25.2 (5.6) years) and healthy controls (27.2 (14.6) years) from Northern India was screened for CCR532 deletion. We found that only 11 of 367 controls were heterozygous for the mutation compared with 17 of 215 with atopic asthma (p = 0.0009). However, we failed to detect any homozygous individual in either group in preliminary analysis. In contrast to previous reports, individuals heterozygous for CCR532 had a 1.6 times greater risk of developing asthma than homozygous wild types.
Since heterozygous individuals may have altered disease susceptibility, we were interested in finding the inheritance pattern of this mutation in the asthmatic families. We therefore recruited 10 families (56 individuals) of the CCR532 heterozygous probands. Genotyping indicated that the mutation segregated in Mendelian fashion. In the process we found two individuals homozygous for this deletion (first report from the Indian subcontinent). Furthermore, to establish the trend of CCR532 in asthmatic families from other parts of India, 36 families (92 individuals) from the north-east and 48 families (147 individuals) from the north-west were also genotyped. Only two members of one family from north-west India were heterozygous for CCR532 deletion while no homo/heterozygous mutants were observed from north-east India.
We suggest that CCR532 is associated with asthma but its low frequency may delay the progress in establishing the role of CCR5 in predicting susceptibility to asthma. Nevertheless, our findings have important implications in understanding the global distribution of CCR532 and its possible impact on the susceptibility to developing various immunological diseases including asthma and AIDS.
References
Loetscher P , Uguccioni M, Bordoli L, et al. CCR5 is characteristic of Th1 lymphocytes. Nature 1998;391:344–5.
Hall IP, Wheatley A, Christie G, et al. Association of CCR5 delta32 with reduced risk of asthma. Lancet 1999;354:1264–5.
Srivastava P , Helms PJ, Stewart D, et al. Association of CCR532 with reduced risk of childhood but not adult asthma Thorax 2003;58:222–6.
Mitchell TJ, Walley AJ, Pease JE, et al. Delta 32 deletion of CCR5 gene and association with asthma or atopy. Lancet 2000;356:1491–2.
Nagy A , Kozma GT, Bojszko A, et al. No association between asthma or allergy and the CCR5Delta 32 mutation. Arch Dis Child 2002;86:426.(J Batra, M Sharma, R Chat)
Correspondence to:
Dr B Ghosh
Molecular Immunogenetics Laboratory, Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India; bghosh@igib.res.in
Keywords: asthma; atopy; CCR5; genetics
Chemokine receptor 5 (CCR5) contributes to the generation of a Th1 immune response by interacting with agonists such as RANTES, MIP-1, and MIP-1?.1 A 32 base pair deletion (32) in CCR5 has been proposed to protect individuals against HIV infection and to bias the immune system towards a Th2-driven response, thus affecting the susceptibility to develop allergic diseases such as asthma. In a study in Scottish children, Hall et al reported an association of CCR532 with a reduced risk of asthma2 but found no such association in adults with asthma.3 In addition, no association was detected with atopy or asthma/wheeze in two other studies.4,5
We examined the potential role for this deletion in the pathogenesis of asthma by an association study in a genetically untapped Indian population. Patients were diagnosed with asthma on the basis of the National Asthma Education and Prevention Program (Expert Panel Report 2) guidelines. Written consent was obtained from individuals participating in the study. Genomic DNA from patients with atopic asthma (mean (SD) age 25.2 (5.6) years) and healthy controls (27.2 (14.6) years) from Northern India was screened for CCR532 deletion. We found that only 11 of 367 controls were heterozygous for the mutation compared with 17 of 215 with atopic asthma (p = 0.0009). However, we failed to detect any homozygous individual in either group in preliminary analysis. In contrast to previous reports, individuals heterozygous for CCR532 had a 1.6 times greater risk of developing asthma than homozygous wild types.
Since heterozygous individuals may have altered disease susceptibility, we were interested in finding the inheritance pattern of this mutation in the asthmatic families. We therefore recruited 10 families (56 individuals) of the CCR532 heterozygous probands. Genotyping indicated that the mutation segregated in Mendelian fashion. In the process we found two individuals homozygous for this deletion (first report from the Indian subcontinent). Furthermore, to establish the trend of CCR532 in asthmatic families from other parts of India, 36 families (92 individuals) from the north-east and 48 families (147 individuals) from the north-west were also genotyped. Only two members of one family from north-west India were heterozygous for CCR532 deletion while no homo/heterozygous mutants were observed from north-east India.
We suggest that CCR532 is associated with asthma but its low frequency may delay the progress in establishing the role of CCR5 in predicting susceptibility to asthma. Nevertheless, our findings have important implications in understanding the global distribution of CCR532 and its possible impact on the susceptibility to developing various immunological diseases including asthma and AIDS.
References
Loetscher P , Uguccioni M, Bordoli L, et al. CCR5 is characteristic of Th1 lymphocytes. Nature 1998;391:344–5.
Hall IP, Wheatley A, Christie G, et al. Association of CCR5 delta32 with reduced risk of asthma. Lancet 1999;354:1264–5.
Srivastava P , Helms PJ, Stewart D, et al. Association of CCR532 with reduced risk of childhood but not adult asthma Thorax 2003;58:222–6.
Mitchell TJ, Walley AJ, Pease JE, et al. Delta 32 deletion of CCR5 gene and association with asthma or atopy. Lancet 2000;356:1491–2.
Nagy A , Kozma GT, Bojszko A, et al. No association between asthma or allergy and the CCR5Delta 32 mutation. Arch Dis Child 2002;86:426.(J Batra, M Sharma, R Chat)