Polymorphisms in the HPC/ELAC-2 and alpha 1-antitrypsin genes that correlate with human diseases in a North Indian population
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Two genes HPC/ELAC-2 and AAT were studied in north Indian population. HPC/ELAC-2 was studied in prostate cancer cases and AAT was studied in COPD patients. HPC/ELAC-2 is considered as an important cancer-susceptibility gene in prostate cancer. There are two common polymorphisms of this gene, i.e., Ser217Leu and Ala541Thr. Alpha 1 antitrypsin is a highly polymorphic anti-elastase enzyme, especially active in the protection of alveoli and liver. In the present study, we observed the distribution of two deficient alleles PiZ and Pi S in COPD patients. We extracted the DNA from 157 prostate cancer cases, 200 COPD patients, 170 BPH and 370 healthy controls. The polymorphisms were studied by PCR–RFLP technique. The mutant genotype (Leu/Leu) of HPC/ELAC-2 was present in 9.6, 7.6 and 5.9% of BPH, cancer cases and healthy controls, respectively. Higher risk of Ser/Leu as well as Leu/Leu had shown when compared to healthy controls. That was about 1.5 and 1.7-fold (OR = 1.55; 95% CI = 0.96–2.51; OR = 1.70; 95% CI = 0.74–3.92), respectively. Risk was found to be increased in smokers and those consuming non-vegetarian diet. Our results suggest that the HPC/ELAC-2 polymorphisms, especially in localized cases, could help to predict prostate cancer risk and confirm its high prevalence of the leu/leu allele in north Indian population. Considering heterozygous PiZ genotype, we obtained an OR of 3.82 (P = 0.03). Multivariate analysis adjusted by age sex and drinking habit showed 4.15-fold increased risk for COPD in PiZ heterozygous individuals. No increased risk was observed in the individuals carrying PiS alleles.
KeywordsProstate cancer HPC/ELAC-2 polymorphisms BPH COPD AAT
We greatly acknowledge the help of the staff and patients of the various hospitals involved. The study was funded by ICMR, Delhi.
- 8.Xu J, Zheng SL, Carpten JD, Nupponen NN, Robbins CM, Mestre J, Moses TY, Faith DA, Kelly BD, Isaacs SD, Wiley KE, Ewing CM, Bujnovszky P, Chang B, Bailey-Wilson JER, Walsh PC, Trent JM, Meyers DA, Isaacs WB (2001) Evaluation of linkage and association of HPC2/ELAC2 in patients with familial or sporadic prostate cancer. Am J Hum Genet 68:901–911PubMedCrossRefGoogle Scholar
- 15.Mastrangeli A, Crystal RG (1996) Alpha 1-antitrypsin: an introduction. In: Crystal RG (ed) Alpha 1-antitrypsin deficiency, biology, pathogenesis, clinical manifestations, therapy. Marcel Dekker, Inc, New York, pp 3–18Google Scholar
- 21.Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, pp 1–18Google Scholar
- 23.Tavtigian SV, Simard J, Teng DHF, Abtin V, Baumgard M, Beck A, Camp NJ, Carillo AR, Chen Y, Dayananth P, Desrochers M, Dumont M, Farnham JM, Frank D, Frye C, Ghaffari S, Gupte JS, Hu R, Iliev D, Janecki T, Kort EN, Laity KE, Leavitt A, Leblanc G, Morrison JM, Pederson A, Penn B, Peterson KT, Reid JE, Richards S, Schroeder M, Smith R, Snyder SC, Swedlund B, Swensen J, Thomas A, Tranchant M, Woodland Ann-Marie, Labrie F, Skolnick MH, Neuhausen S, Rommens J, Cannon-Albright LA (2001) A candidate prostate cancer susceptibility gene at chromosome 17p. Nat Genet 27:172–180PubMedCrossRefGoogle Scholar
- 25.Takahashi H, Lu W, Watanabe M, Katoh T, Furusato M, Tsukino H, Nakao H, Sudo A, Suzuki H, Akakura K, Ikemoto I, Asano K, Ito T, Wakui S, Muto T, Hano H (2003) Ser217Leu polymorphism of the HPC2/ELAC2 gene associated with prostatic cancer risk in Japanese men. Int J Cancer 107:224–228PubMedCrossRefGoogle Scholar
- 38.Silverman EK, Chapman HA, Drazen JM, Weiss ST, Rosner B, Campbell EJ, O’Donnell WJ, Reilly JJ, Ginns L, Mentzer S, Wain J, Speizer FE (1998) Genetic epidemiology of severe, early-onset chronic obstructive pulmonary disease. Risk to relatives for airflow obstruction and chronic bronchitis. Am J Respir Crit Care Med 157:1770–1778PubMedGoogle Scholar