title: Polymorphisms in the pituitary growth hormone gene and its receptor associated with coronary artery disease in a predisposed cohort from India.
abstract: We investigated the promoter polymorphisms of the pituitary growth hormone gene (GH1) and exon 3 deletion polymorphism (GHRd3) in its receptor gene (GHR) in 299 angiographically proven patients with coronary artery disease (CAD) and 231 asymptomatic controls enrolled in the ongoing Indian Atherosclerosis Research Study. Real time PCR based analysis of the GHR variant showed significant association of the GHRd3 deletion allele with CAD (OR 0.48, 95% CI: 0.30-0.76, P = 0.0014) and a dominant model of inheritance (Akaike information criterion = 482). The deletion allele showed significant association with high plasma HDL-c levels (P = 0.001). Sequencing of the proximal promoter region of GH1 revealed 12 novel polymorphisms and a TAGA haplotype constituted by the functional SNPs rs2005171, rs11568828, rs2005172 and rs6171, that showed significant association with CAD alone (adjusted OR of 3.31 (95% CI = 1.33-8.29, P = 0.011) and in CAD patients with diabetes (P = 0.019). Mean standardized height was associated with three of the four haplotype-tagging SNPs in the cohort (P ≤ 0.03). Eleven of the 12 polymorphic promoter SNPs contributed to 14.7% of variation in height in females in the whole dataset (P = 0.029). CAD patients with history of stroke exhibited marginally significantly lower mean height as compared to rest of the cohort (P < 0.006). In conclusion, genetic polymorphisms in the GHR gene and its ligand, GH1, may modulate the risk of CAD in the Asian Indian population.
authors.affiliation: Mary and Garry Weston Functional Genomics Unit, Thrombosis Research Institute India, 258/A, Bommasandra Industrial Area, Bangalore 560 099, India.
authors.forename: Arindam
authors.initials: A
authors.lastname: Maitra
authors.forename: Jayashree
authors.initials: J
authors.lastname: Shanker
authors.forename: Debabrata
authors.initials: D
authors.lastname: Dash
authors.forename: Prathima R
authors.initials: PR
authors.lastname: Sannappa
authors.forename: Shibu
authors.initials: S
authors.lastname: John
authors.forename: Pratibha
authors.initials: P
authors.lastname: Siwach
authors.forename: Veena S
authors.initials: VS
authors.lastname: Rao
authors.forename: H
authors.initials: H
authors.lastname: Sridhara
authors.forename: Vijay V
authors.initials: VV
authors.lastname: Kakkar
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D015331:Cohort Studies; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000235:genetics*; D005260:Female; D005809:Genes, Regulator; D020022:Genetic Predisposition to Disease; D013006:Growth Hormone / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011986:Receptors, Somatotropin / Q000235:genetics*; D020521:Stroke / Q000150:complications
chemical_list: D008076:Cholesterol, HDL; D011986:Receptors, Somatotropin; D013006:Growth Hormone