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17551

Association of ADAM33 Gene Variants' T1, T2 and S1 In Genetic Susceptibility to Asthma and Its Severity In Indian Children

Saturday, October 20, 2012
Room 346-347 (Morial Convention Center)
Priya Tripathi, Pediatrics, Chhtrapati Shahuji Maharaj Medical University, Lucknow, India, Shally Awasthi, MD, Pediatrics, Chhatrapati Shahuji Maharaj Medical University, Lucknow, India and Subramaniam Ganesh, Biological Sciences and Bioengineering,, Iit Kanpur, Kanpur, India

Purpose: A disintegrin and metalloprotease 33 (ADAM33), was the first identified asthma-susceptible gene by positional cloning. Presently, there is a need to study the association of all most common SNPs of ADAM33 with asthma and its severity. Aims of present study were: 1) to assess association of ADAM33 gene polymorphisms (V2 C/T, T2 A/G, T1 A/G, Q-1 A/G, BC+1 A/G and S1 A/G) with asthma and its severity in Indian children 2) In cases, to assess association of all six SNPs with family history of asthma. Methods: This was a case-control study, conducted after approval of institutional ethics committee and patients enrolled after obtaining informed consent of participants/ Guardians. Included were those aged between 1 to 12 years. Diagnosis and severity of asthma were made according to the Global Initiative for Asthma criteria (GINA-2005) guidelines. Controls were age and sex matched non-relatives of cases without any respiratory disease. Genotyping was done by PCR-RFLP method. Results: From august 2007 to September 2009, total of 148 non- asthmatic controls (mean age 73.61months±42.56, 29.9% females) and 234 cases (mean age 74.39months±45.76, 32.2% females) of asthma were recruited , of which 53(22.6%)had mild intermittent, 145(62.0%)had mild persistent and 36(15.4%)had moderate persistent asthma. In our study, we found statistically significant association of SNPs T1, T2 and S1 with asthma (p value <0.05). SNPs T1 and S1 showed statistically significant association with severity subgroups of asthma as compared with controls. Significant association found between mutant genotype of all studied SNPs and family history of asthma (Table1).

Table 1 Association of mutant genotype of studied polymorphisms of ADAM33 gene with positive family history of asthma

Mutant Genotypes

Family History of Asthma

OR, (CI 95%), P Value

 

Present(101); Total cases (234)

 

V2,  C/T (TT)

45(44.6)

2.9(1.6-5.3)0.0002

T2, A/G (GG)

49(48.5)

2.1(1.2-3.8)0.006

T1, A/G (GG)

67(66.3)

13.5(6.7-27.4)<0.0001

Q-1, A/G (GG)

95(94.1)

6.3(2.4-17.6)<0.0001

S1, A/G (GG)

52(51.5)

2.1(1.2-3.7)0.007

BC+1, A/G (GG)

76(75.2)

1.9(1.1-3.6)0.021

  Conclusion: There is an association of ADAM33 SNPs (T1, S1, T2 and V2) with asthma in Indian pediatric population; we also observed association of mutant genotype of all studied six SNPs’ with family history of asthma, but only T1 and S1 were found to be associated with disease severity.