title: Genetic determinants of chronic obstructive pulmonary disease in South Indian male smokers.
abstract: The development of chronic obstructive pulmonary disease, upon exposure to tobacco smoke, is the cumulative effect of defects in several genes. With the aim of understanding the genetic structure that is characteristic of our patient population, we selected forty two single nucleotide polymorphisms of twenty genes based on previous studies and genotyped a total of 382 samples, which included 236 patients and 146 controls using Sequenom MassARRAY system. Allele frequencies of rs2276109 (MMP12) and rs1800925 (IL13) differed significantly between patients and controls (p = 0.013 and 0.044 respectively). Genotype analysis showed association of rs2276109 (MMP12) under additive and dominant models (p = 0.017, p = 0.012 respectively), rs1800925 (IL13) under additive model (p = 0.047) and under recessive model, rs1695 (GSTP1; p = 0.034), rs729631, rs975278, rs7583463 (SERPINE2; p = 0.024, 0.024 and 0.012 respectively), rs2568494, rs10851906 (IREB2; p = 0.026 and 0.041 respectively) and rs7671167 (FAM13A; p = 0.029). The minor alleles of rs1695 (G), rs7671167 (T), rs729631 (G), rs975278 (A) and rs7583463 (A) showed significant negative association whereas those of rs2276109 (G), rs2568494 (A), rs10851906 (G) and rs1800469 (T; TGF-β) showed significant positive association with lung function under different genetic models. Haplotypes carrying A allele of rs2276109, G allele of rs1695 showed negative correlation with lung function. Haplotypes carrying major alleles of rs7671167 (C) of FAM13A and rs729631 (C), rs975278 (G), rs7583463 (C) of SERPINE2 had protective effect on lung function. Haplotypes of IREB2 carrying major alleles of rs2568494 (G), rs2656069 (A), rs10851906 (A), rs965604 (C) and minor alleles of rs1964678 (T), rs12593229 (T) showed negative correlation with lung function. In conclusion, our study replicated the results of most of the previous studies. However, the positive correlation between the minor alleles of rs2568494 (A) and rs10851906 (G) of IREB2 and lung function needs further investigation.
authors.affiliation: Department Of Anthropology, Division Of Human Genetics, Sri Venkateswara University, Tirupati, Andhra Pradesh, India.
authors.forename: Cholendra
authors.initials: C
authors.lastname: Arja
authors.affiliation: Department Of Human Genetics, Punjabi University, Patiala, Punjab, India.
authors.forename: Rajasekhara Reddy
authors.initials: RR
authors.lastname: Ravuri
authors.affiliation: Anthropological Survey Of India, Southern Regional Centre, Mysore, Karnataka, India.
authors.forename: Venugopal N
authors.initials: VN
authors.lastname: Pulamaghatta
authors.affiliation: Department Of Biochemistry, Saveetha Medical College & Hospital, Faculty Of Medicine, Saveetha University, Chennai, Tamil Nadu, India.
authors.forename: Krishna Mohan
authors.initials: KM
authors.lastname: Surapaneni
authors.affiliation: Premananda Allergy And Chest Hospital, Tirupati, Andhra Pradesh, India.
authors.forename: Premanand
authors.initials: P
authors.lastname: Raya
authors.affiliation: Anthropological Survey Of India, Southern Regional Centre, Mysore, Karnataka, India.
authors.forename: Chandrasekhar
authors.initials: C
authors.lastname: Adimoolam
authors.affiliation: Department Of Anthropology, Division Of Human Genetics, Sri Venkateswara University, Tirupati, Andhra Pradesh, India.
authors.forename: Kodanda Reddy
authors.initials: KR
authors.lastname: Kanala
mesh_terms: D020690:GTPase-Activating Proteins / Q000235:genetics; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007194:India; D035942:Iron Regulatory Protein 2 / Q000235:genetics*; D016014:Linear Models; D008297:Male; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics*; D058258:Serpin E2 / Q000235:genetics; D012907:Smoking / Q000009:adverse effects*
chemical_list: C570078:FAM13A protein, human; D020690:GTPase-Activating Proteins; C545486:SERPINE2 protein, human; D058258:Serpin E2; D035942:Iron Regulatory Protein 2