Background: An inappropriate increase in peripheral vascular resistance relative to the cardiac output is a cause of essential hypertension. Numerous genetic markers have been identified in the regulation of blood pressure and essential hypertension. Alpha adducin (ADD1) is one such marker. ADD1 protein, found in the renal tubule, is involved in cellular signal transduction and interacts with other membrane skeleton proteins that affect ion transport across the cell membrane. Mutated ADD1 may affect the regulation of some factors in the Na transport system in the luminal part of the cell. So, ADD1 can be considered as a ‘renal hypertensive gene’ that affects the capacity of the tubular epithelial cell to transport Na and hence, affects blood pressure. Diuretic agents are drugs that increase renal excretion of water and solutes (mainly sodium salt).The Gly460Trp variant of the alpha-adducin gene influences the constitutive capacity of the kidney to reabsorb sodium, thus implying a modulation of the Blood pressure responsiveness to a diuretic ,which inhibits such renal mechanism. Thus, yielding diuretics a more beneficial therapeutic effect. Aims and objective: This study is to carried out for survey of SNPGly460Trp prevalent among hypertensive patients from Punjab and role of ADD1 gene variant rs4961 in causation of any other metabolic disorder. Materials and methods: Genotyping of SNPs predicted by Insilco analysis of this gene sequences will be done through RFLP-PCR analysis. Results: In silico analysis reports that the SNP, rs4961 expressing the amino acid variant (G460W) has significant damaging effect and can be considered to be functionally important. The allelic distribution of ADD1 rs4961 showed, this locus was found to be polymorphic in Punjabi population. it was found significantly associated with hypertension in Punjabi population. Mutant allele of rs4961 is not responsible for causation of any other metabolic disorder in hypertensive patients. but muatant allele T shows significant results with causation of other metabolic disorders in patients under diuretic therapy.(p=0.035) Conclusion: This study can be a way to “measure” the overall clinical impact of the ADD1 Trp allele and then to estimate the size of the population that may be affected by this genetic mechanism is to apply a very selective pharmacologic tool that is able to interfere with the sequence of events that are triggered by this allele
