Important Variant Information for HMGCR
Submitted by: Marisa Wong Medina(PARC)
Reviewed by: Issam Zineh(PEAR)
Submitted date: February 6, 2006
There are Two Important Variants for HMGCR
1. HMGCR:SNP 12(rs17244841)
2. HMGCR:SNP 29(rs17238540)
| Gene HGNC Name: | HMGCR |
|---|---|
| Variant Summary: | Also known as SNP12, the estimated allele frequencies of this variant in the predominantly Caucasian PRINCE population (88.7%) are: A=0.965 and T=0.035. In a study of 1536 individuals, SNP12 was significantly associated with the mean change in both total and LDL-cholesterol. Heterozygous individuals had a 21.8% reduction in total cholesterol lowering and a 19.0% reduction in LDL-cholesterol lowering after pravastatin treatment as compared to individuals homozygous for the major (A) allele. There was no genotype effect on HDL-cholesterol changes. These effects remained significant after multiple testing, were not associated with baseline differences, and the LDL-cholesterol effect became stronger after ethnic stratification [PMID: 15199031]. |
| Key PubMed IDs: | 15199031 |
| Genomic Variant & GenBank ID: | 11898 A>T on AY321356 |
| mRNA Variant & GenBank ID: | Intronic SNP; no mRNA change |
| Protein Variant & GenBank ID: | Intronic SNP; no protein change |
| dbSNP rs#: | rs17244841 |
| GoldenPath Position: | Chr5: 74,678,611 (hg18) |
| Key Drugs/Substrates: | Pravastatin [PMID: 15199031] |
| Key Phenotypes/Diseases: | Attenuated cholesterol reduction with pravastatin treatment [PMID: 15199031] |
| DNA Source Containing Homozygous Reference Allele(Coriell Lines): |
White (European): PA126741408 (NA12547), PA126741328 (NA10845), PA126740852 (NA10853), PA126743895 (NA10860), PA126743912 (NA10830), PA126740847 (NA10842), PA126740850 (NA10851), PA126741308 (NA07349), PA126743882 (NA10857), PA126743959 (NA10858), PA126743926 (NA10848), PA126741327 (NA10844), PA126740853 (NA10854), PA126743896 (NA10861), PA126743913 (NA10831), PA126743958 (NA10843), PA126740849 (NA10850), PA126743881 (NA10852), PA126743853 (NA06990), PA126741276 (NA07019) Black or African American (African American): PA126746650 (NA17103), PA126746655 (NA17104), PA126746659 (NA17105), PA126746664 (NA17106), PA126746666 (NA17107), PA126746675 (NA17110), PA126746676 (NA17111), PA126746677 (NA17112), PA126746678 (NA17113), PA126746689 (NA17114), PA126746700 (NA17116), PA126746722 (NA17133), PA126746723 (NA17134), PA126746724 (NA17135), PA126746725 (NA17136), PA126746726 (NA17137), PA126746727 (NA17138), PA126746728 (NA17139), PA126746729 (NA17140) |
| DNA Source Containing Heterozygous Reference Allele(Coriell Lines): |
White (European): PA126741307 (NA07348) Black or African American (African American): PA126746644 (NA17101), PA126746648 (NA17102), PA126746670 (NA17108) |
| Key Haplotypes: | H7 |
| Gene HGNC Name: | HMGCR |
|---|---|
| Variant Summary: | Also known as SNP29, the estimated allele frequencies of this variant in the predominantly Caucasian PRINCE population (88.7%) are: T=0.965 and G=0.035. The ACCESS trial reported a minor allele frequency of 0.0 in Asians (N=36), 0.085 in African Americans (N=160), 0.027 in Caucasians (2454) and 0.029 in Hispanics (N=85). In the PRINCE study of 1536 individuals, SNP29 was significantly associated with the mean change in both total and LDL-cholesterol. Heterozygous individuals had a 22.3% reduction in total cholesterol lowering and a 19.0% reduction in LDL-cholesterol lowering after pravastatin treatment as compared to individuals homozygous for the major allele. There was no genotype effect on HDL-cholesterol changes. These effects remained significant after multiple testing, were not associated with baseline differences, and the LDL-cholesterol effect became stronger after ethnic stratification [PMID: 15199031]. The ACCESS trial was unable to validate the association between SNP29 and LDL-cholesterol lowering in 293 Caucasian individuals treated with pravastatin for 24-weeks. In addition, the trial included 1902 individuals were treated with atorvastatin, 477 individuals with fluvastatin, 476 individuals with lovastatin, and 468 individuals with simvastatin, and no other significant associations between SNP29 and statin efficacy were reported [PMID: 16103896]. |
| Key PubMed IDs: | 15199031, 16103896 |
| Genomic Variant & GenBank ID: | 24558 T>G on AY321356 |
| mRNA Variant & GenBank ID: |
Intronic SNP; no mRNA change |
| Protein Variant & GenBank ID: |
Intronic SNP; no protein change |
| dbSNP rs#: | rs17238540 |
| GoldenPath Position: | chr5:74,691,254 (hg18) |
| Key Drugs/Substrates: | pravastatin [PMID: 15199031, 16103896], atorvastatin, fluvastatin, lovastatin and simvastatin[PMID: 16103896] |
| Key Phenotypes/Diseases: | Attenuated cholesterol reduction with pravastatin treatment [PMID: 15199031] |
| DNA Source Containing Homozygous Reference Allele(Coriell Lines): |
White (European): PA126741408 (NA12547), PA126741328 (NA10845), PA126743895 (NA10860), PA126743912 (NA10830), PA126740850 (NA10851), PA126741308 (NA07349), PA126743959 (NA10858), PA126743926 (NA10848), PA126741409 (NA12548), PA126741327 (NA10844), PA126740853 (NA10854), PA126743896 (NA10861), PA126743913 (NA10831), PA126743958 (NA10843), PA126740849 (NA10850), PA126743881 (NA10852), PA126743853 (NA06990), PA126741276 (NA07019) Black or African American (African American): PA126746650 (NA17103), PA126746659 (NA17105), PA126746664 (NA17106), PA126746666 (NA17107), PA126746672 (NA17109), PA126746675 (NA17110), PA126746676 (NA17111), PA126746678 (NA17113), PA126746689 (NA17114), PA126746690 (NA17115), PA126746700 (NA17116), PA126746722 (NA17133), PA126746724 (NA17135), PA126746725 (NA17136), PA126746726 (NA17137), PA126746727 (NA17138), PA126746728 (NA17139) |
| DNA Source Containing Heterozygous Reference Allele (Coriell Lines): |
White (European): PA126741421 (NA12560), PA126741307 (NA07348) Black or African American (African American): PA126746644 (NA17101), PA126746648 (NA17102), PA126746670 (NA17108), PA126746729 (NA17140) |
| Key Haplotypes: | H7 |