Promethease Report

rs4363657 is a SNP in the SLCO1B1 gene, a gene which encodes a protein involved in the liver's uptake of certain drugs, including the statins used to lower cholesterol levels. rs4363657 in nearly complete linkage disequilibrium with rs4149056 SNP (r<sup>2</sup>=0.97), which has been linked to statin metabolism. rs4149056(C) odds ratio for myopathy among 20,000 individuals taking either 40 or 80mg of simvastatin daily was 4.5 (CI: 2.6-7.7) per copy of the C allele, and 16.9 (CI: 4.7-61.1) in (C;C) as compared with (T;T) homozygotes. See also rs4149056 for a more detailed description of the effect of SLCO1B1 gene SNPs on the metabolism of many drugs.

[http://spittoon.23andme.com/2008/10/13/snpwatch-two-groups-discover-dna-variations-linked-to-male-pattern-baldness/ spitoon] rs2180439(T;T) have 2x increased odds of male pattern baldness.

This SNP influences skin pigmentation. The allele p.A111T, rs1426654(A), indicates light-skinned european ancestry. [PMID 16847698, PMID 16357253] It appears as if this SNP is a relatively new one in human evolution; one estimate is that the rs1426654(A) allele, in other words, light skin pigmentation, spread through the European population around 6,000 - 12,000 years ago. Prior to that, 'European ancestors' were most likely relatively brown-skinned.

This SNP, located in an intron of the LOXL1 gene, was initially reported to be associated with exfoliation glaucoma. However, it was shown in the same study to no longer be significant once two other SNPs, which cause actual changes in the LOXL1 protein, were identified. More specifically, the risk allele rs2165241(T) was found to be associated with glaucoma only because it effectively predicted (with 90% probability) the actual high-risk haplotype consisting of rs1048661(G) and rs3825942(C), as oriented with respect to their entries in dbSNP. rs2165241 was significantly associated with XFG and XFS (p=4.13x10e-9 for an additive model, heterozygote odds ratio = 4.42 (CI: 2.3-8.5), homozygote odds ratio = 34.19 (CI: 4.48-261), with the rs2165241 (T) allele being the risk allele, found in 8...

rs4149056 is a SNP in the SLCO1B1 gene, which encodes the 'organic anion transporting polypeptide 1B1' (OATP1B1) protein. This protein, found primarily in the liver, regulates the uptake of numerous drugs and natural compounds. The rs4149056(C) allele gives rise to an amino acid change (from valine to alanine at residue 174) which has reduced uptake/transport activity. Therefore, drugs metabolized by OATP1B1 tend to build up to higher circulating concentrations than they would otherwise.. The drugs known (or in some cases, thought) to be transported less well by the variant OATP1B1 protein encoded by the rs4149056(C) allele include: *Several cholesterol lowering statins, generally leading to reduced inhibitory effects on liver cholesterol synthesis and possibly worse side effects, by such ...

rs601338 is found on chromosome 19 in the alpha(1,2)-fucosyltransferase FUT2 gene. The wild-type rs601338(G) encodes the 'Secretor' (Se) allele, while rs601338(A) encodes the 'nonsecretor' (se) allele. A study of 115 Swedish adults concluded that rs601338(A;A) homozygotes have genetic immunity to infection by the Norwalk norovirus, a major (and contagious) cause of acute gastroenteritis worldwide among adults.(PMID 12692541) (PMID 16306606)

Category:interesting This snp (and perhaps its neighbors) may influence intelligence and alcohol dependence and or this [http://www.tweelingenregister.org/nederlands/verslaggeving/congresbezoek/Gosso_ESHG_2006.pdf pdf poster] show association between the CHRM2 gene and intelligence . In this study of ~300 Caucasians, the (T;T) genotype appeared to typically have a 4 point higher IQ than the (A;T) genotype, which had a 4 point higher IQ (on average) than the (A;A) genotype. A nearby SNP, rs324640, showed similar results to rs324650, and was in linkage disequilibrium (r2 = 0.90) with it. CHRM2 gene predisposes to alcohol dependence, drug dependence and affective disorders: results from an extended case-control structured association study. And the earlier

This SNP (C/T) is in 5' region of the HLA-C gene, 35 kb away from transcription initiation in or around the HLA-C gene. 'People with this tiny sequence variation, dubbed rs9264942, appear to have up to 90% less virus in their systems than those who carry other polymorphisms. About 10% of Europeans appear to carry two copies of rs9264942, which leads to an average 90% viral load reduction. About 50% of Europeans carry one copy, which gives a 60% reduction. By comparison, less than 40% of people of African descent appear to carry a single copy of the polymorphism.' [http://www.newscientist.com/article/dn12297-genetic-variation-may-lower-hiv-load-by-90.html Genetic variation may lower HIV load by 90%] They are referring to the (C;C) genotype giving a 90% reduction and the (C;T) giving a 60% r...

This SNP, in the ACTN3 gene, encodes a premature stop codon in a protein likely to be important in muscle function. The polymorphism alters position 577 of the alpha-actinin-3 protein, and while the most common nucleotide at this position, (C), encodes an arginine (amino acid code R), the stop codon is refered to as X. Hence, the SNP is referred to as R577X, with homozygotes being either RR or XX and heterozygotes being RX. The main report studying a relatively small number of Australian elite (ie ~Olympic) athletes found that, at least in females, the R allele (ie rs1815739(C)) is associated with sprinters, while the X allele (rs1815739(T)) is associated with endurance athletes. No female or Olympic-level sprinters were XX homozygotes (rs1815739(T;T)). The association tended the same way ...

rs6604026 has been reported in a large study to be associated with multiple sclerosis. The risk allele (oriented to the dbSNP entry) is (C); the odds ratio associated with this allele is 1.15 (CI 1.08-1.22).

[omim:PROSTATE CANCER, SUSCEPTIBILITY TO]

[omim:PEPTIDE TRANSPORTER PSF2 POLYMORPHISM]

A large study of Caucasian children has identified this SNP in the TBX21 gene (and one other, rs16947078) as defining a haplotype associated with increased risk for allergic asthma. The odds ratio associated with rs11650354(T;T) homozygotes compared to rs11650354(C;C) homozygotes for allergic asthma is reported to be 8.13 (CI: 2.5-26.9). Heterozygotes may be at slightly higher risk.

rs10494366, a SNP in the NOS1AP gene encoding the nitric oxide synthase I protein, accounts for some of the variation seen in abnormal heart rhythms, in particular, the QT interval. Based on studies totaling ~4,000 individuals of Caucasian ancestry, homozygotes for one allele have shorter QT intervals, while homozygotes for the other allele have a longer QT interval. A follow-up study determined that one rs10494366(G) allele was associated with a 3.8-ms (CI: 3.0 - 4.6ms, p=7.8x10(-20)) increase in QT interval duration, and two (G) alleles had twice that increase. No increase in risk for sudden death due to a cardiac problem was associated with this SNP, though. rs10494366 minor homozygotes had a 9.3 msec longer QT interval compared to major homozygotes (p=5.7x10(-5)); rs10918594 minor h...

In a Swiss cohort: 'Carriers of KIBRA rs17070145 T allele had 24% better free recall performance 5 min after word presentation (P = 0.000004) and 19% better free recall performance 24 hours after word presentation (P = 0.0008) than did noncarriers.' In a US cohort: 'T allele carriers had significantly better memory scores than non-carriers in the Buschke's Selective Reminding Test (SRT). Performance on another episodic memory task, the Rey Auditory Verbal Learning Test (AVLT), was also significantly different between allele groups.' In another Swiss cohort, with a visual episodic memory task: 'T allele carriers also performed significantly better than did noncarriers in this population.' 'Functional magnetic resonance imaging detected KIBRA allele-dependent differences in hippocampal activ...

rs17576, also known as Gln279Arg or Q279R, is a SNP in exon 6 of the matrix metalloproteinase-9 MMP9 gene. The rs17576(G) allele encodes the Arg (R). In a study of 385 male veterans with greater than 20 pack-years of cigarette smoking, rs17576(G) allele carriers were at higher risk for chronic obstructive pulmonary disease (COPD). The rs17576(G;G) homozygous genotype was at 3-fold increased risk for COPD. A study of 744 Chinese patients with lung cancer found that the rs17576(G;G) genotype was associated with higher risk of lung cancer with metastasis (adjusted OR, 1.79, CI: 1.03-3.08) compared to the (A;A) genotype. rs17576 is also one of two SNPs in the MMP9 gene associated with increased risk for myocardial infarction, but not coronary artery disease. The relatively weak odds ratios for...

SNP rs2201841, in the IL23R gene, is associated with increased risk for Crohn's disease in both Jewish and non-Jewish populations. Another study found that the 'A allele' and 'AA genotype' were significantly overrepresented in Graves' disease patients with Graves ophthalmopathy, based on 216 North American patients. The odds ratios reported were 2.04 for the allele (p=1x10<sup>-4</sup>), and for the so-called 'AA' genotype (presumably rs2201841(T;T) when correctly oriented to the dbSNP orientation), 2.4 (p=1x10<sup>-4</sup>).

rs1800497, a SNP also known as the TaqIA (or Taq1A) polymorphism of the dopamine D2 receptor DRD2 gene (even though it is actually located over 10,000bp downstream of the gene), gives rise to the DRD2*A1 allele. This allele (rs1800497(T)) is associated with a reduced number of dopamine binding sites in the brain , and has been postulated to play a role in alcoholism, smoking, and certain neuropsychiatric disorders. The reduced number of dopamine binding sites may play a role in nicotine addiction by causing an 'understimulated' state that can be relieved by smoking (and/or use of other drugs). A wide variety of reports have been published over more than ten years either linking rs1800497 to aspects of nicotine use and smoking cessation success, or finding no such association. A meta-analy...

The (A) allele of rs326 was associated with risk for lower high-density lipoprotein (HDL) cholesterol plasma levels in 3 independent population samples, including both Caucasians and African-Americans.

rs6457617 has been reported in a large study to be associated with rheumatoid arthritis. This SNP is reported to be the most statistically significant of many SNPs similarly located in the MHC region. The risk allele (oriented to the dbSNP entry) is (T); the odds ratio associated with heterozygotes is 2.36 (CI 1.97-2.84), and for homozygotes, 5.21 (CI 4.31-6.30).

The G->C (Cys2229Ser) polymorphism (rs619203) of the ROS1 gene was significantly associated with atherothrombotic cerebral infarction in a study of 3,400+ Japanese adults. rs619203 increases susceptibility to Myocardial Infarction 1.15 times for heterozygotes (CG) and 1.75 times for homozygotes (TT)