Suggestive evidence of association of C-159T functional polymorphism of the CD14 gene with atopic asthma in northern and northwestern Indian populations

CD14 is a lipopolysaccharide receptor known to be an important modulator of Th1–Th2 response during early childhood. Genetic association studies of the CD14 gene with asthma and atopic disorders have shown positive as well as negative results in different ethnic populations. The aim of this study was to test for association of C-159T functional promoter polymorphism with atopic asthma and serum IgE levels in northern and northwestern Indian populations. DNA was assayed for the CD14 C-159T polymorphism in a case-control study involving atopic asthmatics (n=187) and healthy normal controls (n=227), and in a family-based association study of 106 trios. The case-control study showed an association at the genotypic (P=0.0146) as well as the allelic level (P=0.0048). Moreover, we observed a deviation of allelic transmission from random proportions (P=0.024) in the transmission disequilibrium test analysis. When we analyzed our results for serum total IgE levels, against this polymorphism, we observed a difference at the genotypic (P=0.0026) as well as at the allelic level (P=0.0016) in a case-control study, whereas no association in the quantitative transmission disequilibrium test analysis was obtained. These findings provide suggestive evidence of association of the CD14 gene locus with atopic asthma in northern and northwestern Indian populations.

[1]  S. Holgate.  Genetic and environmental interaction in allergy and asthma☆☆☆ , 1999, Journal of Allergy and Clinical Immunology.

[2]  P. Sly,et al.  Atopic versus infectious diseases in childhood: a question of balance? , 1997, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[3]  B. Ghosh,et al.  Association of IFNG gene polymorphism with asthma in the Indian population. , 2002, The Journal of allergy and clinical immunology.

[4]  T. Kurz,et al.  Promoter polymorphisms of the CD14 gene are not associated with bronchial asthma in Caucasian children. , 2003, European journal of immunogenetics : official journal of the British Society for Histocompatibility and Immunogenetics.

[5]  D. Vercelli,et al.  Engagement of CD14 on monocytes inhibits the synthesis of human Igs, including IgE. , 1994, Journal of immunology.

[6]  G. Abecasis,et al.  A general test of association for quantitative traits in nuclear families. , 2000, American journal of human genetics.

[7]  W. Cookson,et al.  The alliance of genes and environment in asthma and allergy , 1999, Nature.

[8]  M. Jenmalm,et al.  Reduced levels of soluble CD14 in atopic children , 2004, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[9]  R. Rossaint,et al.  Lack of association between the –260 C→T promoter polymorphism of the endotoxin receptor CD14 gene and the CD14 density of unstimulated human monocytes and soluble CD14 plasma levels , 2001, Intensive Care Medicine.

[10]  P. McKeigue,et al.  For Personal Use. Only Reproduce with Permission from the Lancet Publishing Group. Problems of Reporting Genetic Associations with Complex Outcomes , 2022 .

[11]  D. P. Strachan,et al.  Hay fever, hygiene, and household size. , 1989, BMJ.

[12]  J. D. Neely,et al.  Linkage analysis of IL4 and other chromosome 5q31.1 markers and total serum immunoglobulin E concentrations. , 1994, Science.

[13]  B. Ghosh,et al.  Association of IL4 Gene Polymorphisms with Asthma in North Indians , 2004, International Archives of Allergy and Immunology.

[14]  C. Karp,et al.  A Common Single Nucleotide Polymorphism in the CD14 Promoter Decreases the Affinity of Sp Protein Binding and Enhances Transcriptional Activity1 , 2001, The Journal of Immunology.

[15]  D. Postma,et al.  Association of a promoter polymorphism of the CD14 gene and atopy. , 2001, American journal of respiratory and critical care medicine.

[16]  J K Hewitt,et al.  Combined linkage and association sib-pair analysis for quantitative traits. , 1999, American journal of human genetics.

[17]  V. Znojil,et al.  Two CD14 promoter polymorphisms and atopic phenotypes in Czech patients with IgE‐mediated allergy , 2003, Allergy.

[18]  E. Lander,et al.  Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results , 1995, Nature Genetics.

[19]  W. Cookson,et al.  Allergy to Dermatophagoides in a Group of Spanish Gypsies: Genetic Restrictions , 2001, International Archives of Allergy and Immunology.

[20]  S. Weiland,et al.  A promoter polymorphism in the CD14 gene is associated with elevated levels of soluble CD14 but not with IgE or atopic diseases , 2004, Allergy.

[21]  P. Holt,et al.  Serum total IgE levels and CD14 on chromosome 5q31 , 1999, Clinical genetics.

[22]  F. Martinez,et al.  Review article CD14: an example of gene by environment interaction in allergic disease , 2002, Allergy.

[23]  S. Lau,et al.  Evaluation of the CD14 C‐159 T polymorphism in the German Multicenter Allergy Study cohort , 2003, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[24]  F. Martinez,et al.  The Monocyte/IgE Connection: May Polymorphisms in the CD14 Gene Teach Us about IgE Regulation? , 2001, International Archives of Allergy and Immunology.

[25]  A. Tsalenko,et al.  A second-generation genomewide screen for asthma-susceptibility alleles in a founder population. , 2000, American journal of human genetics.

[26]  P. Holt,et al.  A Polymorphism* in the 5' flanking region of the CD14 gene is associated with circulating soluble CD14 levels and with total serum immunoglobulin E. , 1999, American journal of respiratory cell and molecular biology.

[27]  S. Weiss,et al.  Association studies in asthma genetics. , 2001, American journal of respiratory and critical care medicine.