Variant:
chr20:48184659 in PTGIS VIP

Associated with Gene

PTGIS

Allele Frequencies

Based on data from the HapMap project, version 2010-08_phaseII+III.
More information on HapMap populations.

VIP Variant in PTGIS

The variable-number tandem repeat polymorphism (VNTR) in the 5' promoter region is the most widely studied polymorphism in the PTGIS gene. The alleles varied in size, ranging from three to seven repeats of nine base pairs (5' CCGCCAGCC 3'), with six repeats as the most frequent genotype [Article:11281454]. This region of the PTGIS gene is thought to act as a transcription binding factor site for both Sp1 and Ap2 transcription factors in the promoter region of PTGIS. Variation in the number of repeats alters the number of Sp1/Ap2 binding sites. Functional assessment has shown that the transcriptional activity increases with the number of repeats upon stimulation with pro-inflammatory mediators [Article:11281454]. Luciferase reporter assay using human umbilical vein endothelial cells also indicated that the promoter activities of the alleles with three and four repeats (R3, R4) were significantly lower than those of the alleles with five, six and seven repeats (R5, R6 and R7) following IL-6 stimulation [Article:10577996].

Phenotypically, tandem repeat variants in the PTGIS promoter region are associated with vascular diseases such as systolic hypertension and cerebral infarction [Articles:10577996, 11130769]. Specifically, a large case and control study consisting of 4971 participants showed a positive correlation between this polymorphism and hypertension in a Japanese population [Article:10577996]. Individuals with the shorter repeat genotype (R3R3, R3R4, R4R4) or SS genotype, had significantly higher systolic pressure and pulse pressure, compared to individuals with longer repeats. Participants with the SS genotype were also more likely to undergo antihypertensive treatments. In addition, Nakayama T. et al. found that the patients with small number of repeats in the promoter region tend to have higher risk for cerebral infarction in a study with 263 Japanese participants [Article:11130769]. More recently, the VNTR polymorphism in the promoter region of PTGIS was implicated in carcinogenesis. Poole et al. showed that the fewer repeat genotype was associated with a modestly increased risk of adenomas and colorectal polyps, suggesting a possible role of prostacyclin synthase in colon carcinogenesis [Article:16537708].

Citation
M. Whirl-Carrillo, E.M. McDonagh, J. M. Hebert, L. Gong, K. Sangkuhl, C.F. Thorn, R.B. Altman and T.E. Klein. "Pharmacogenomics Knowledge for Personalized Medicine" Clinical Pharmacology & Therapeutics (2012) 92(4): 414-417. Full text
Drugs / Other Molecules
Biological Intermediate (1)
prostaglandin H2
Diseases Adenoma Cerebral Infarction Hypertension Polyps

Appendix

1. PTGIS: 9 bp tandem repeat polymorphism

Genomic Variant & GenBank ID: 77(CCGCCAGCC)6 >(CCGCCAGCC)4 on AF296674
mRNA Variant & GenBank ID: NA
Protein Variant & GenBank ID: NA
dbSNP rs#: NA
GoldenPath Position: chr20:47618066-47618101;(hg18);(for (CCGCCAGCC)4 allele)

Connected Diseases

Cross-References

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