Table 1.
Summary of pharmacogenomic studies of caffeine indicating variants or alleles tested, phenotypes associated, and details of type of caffeine and population
| Allele/genotype | Associated phenotype | Reference | Study parameters |
|---|---|---|---|
|
CYP1A2 rs762551
| |||
| *1F/*1F haplotype, rs762551 Genotype AA |
Increased caffeine metabolism compared with non-*1F carriers |
17370067 [12] | Caffeine intake: 100 mg caffeine dose Study number and race: Swedish smokers, n= 35 (the effect was not seen in Swedish nonsmokers, or in a cohort of Korean smokers, n =28 with low *1F allele frequency) |
| rs762551 Genotype AA |
Increased caffeine metabolism | 20390257 [13] | Caffeine intake: heavy coffee consumers (the association was not seen in nonheavy consumers) Study number and race: Swedish, n= 42, Serbian, n=17 |
| rs762551 Allele C |
Not associated with habitual consumption of caffeine |
17616786 [14] | Caffeine intake: habitual consumption of caffeine Study number and race: Hispanic Americans (n= 2735) |
| rs762551 Genotype CC |
Decreased risk of Parkinson’s disease in coffee drinkers compared with genotype AA |
21281405 [15] | Caffeine intake: association was seen in coffee consumers compared with those who never consume coffee Study number and race: mixed population, n= 948 cases, n= 1286 controls |
| rs762551 | Not associated with caffeine-related protection from Parkinson’s disease |
18759349 [16] | Caffeine intake: coffee drinking habits assessed Study number and race: mixed population, n= 782 matched case–control pairs |
| rs762551 | Not associated with caffeine-related protection from Parkinson’s disease |
18075470 [17] | Caffeine intake: caffeine consumption Study number and race: Asian, n= 418 cases, n =468 controls |
| rs762551 Genotype CC and AC |
Increased risk of myocardial infarction in coffee consumers |
16522833 [18] | Caffeine intake: coffee intake questionnaire Study number and race: Hispanic Americans, n=2104 cases, n=2104 controls |
| rs762551 Genotype CC and AC |
Decreased risk of breast cancer, in carriers of BRCA1 mutations |
17507615 [19] | Caffeine intake: coffee consumption (either caffeinated or decaffeinated), compared with individuals who have never consumed coffee Study number and race: White, n=89 cases and n= 49 controls (coffee consumers) vs. n= 30 controls and n= 36 cases (never consumed coffee) |
| rs762551 | Not associated with risk of ovarian cancer and caffeine, coffee, or tea intake |
18941913 [20] | Caffeine intake: high vs. low caffeine consumption Study number and race: n =1354 cases, n =1851 controls (unknown race) |
| rs762551 | Not associated with risk of bladder cancer and coffee consumption |
18798002 [21] | Caffeine intake: coffee consumption (cups per day) Study number and race: Spanish, n= 1034 cases, n= 911 controls |
| rs762551 Genotype CC |
Increased risk of recurrent pregnancy loss | 15849225 [22] | Caffeine intake: maternal coffee consumption Study number and race: Japanese, n= 58 cases, n= 148 controls |
| rs762551 Genotype CC and AC |
Increased risk for neural tube defects | 20641098 [23] | Caffeine intake: maternal coffee consumption Study number and race: mixed population, n= 306 cases, n= 669 controls |
|
CYP1A2 Alleles
| |||
| *1K allele (Key SNP: –730C>T rs12720461) |
Reduced caffeine metabolism, compared with *1A, *1F, or *1J alleles |
12920202 [24] | Caffeine intake: 100 mg caffeine dose Study number and race: Ethiopian, n =173 (association only seen in nonsmokers, n =153) |
| *1A, *1F, *1J | No significant effect on caffeine metabolism | 12920202 [24] | Caffeine intake: 100 mg caffeine dose Study number and race: Ethiopians, n =173 (nonsmokers: n= 153, smokers, n= 20) |
| *1A, *1D, *1L, *1V, *1W alleles |
No significant effect on caffeine metabolism | 17370067 [12] | Caffeine intake: 100 mg caffeine dose Study number and race: Swedes, n =114 (nonsmokers), n= 35 (smokers), Koreans, n =121 (nonsmokers), n= 28 (smokers) |
|
Additional CYP1A2 variants
| |||
| rs2470890 Genotype CC |
Decreased risk of Parkinson’s disease in coffee drinkers |
21281405 [15] | Caffeine details: coffee consumption Study number and race: mixed population, n= 941 cases, n= 1264 controls |
| rs35694136 | Not associated with caffeine-related protection from Parkinson’s disease |
18759349 [16] | Caffeine intake: coffee drinking habits assessed Study number and race: mixed population, n= 910 matched case–control pairs |
| rs2470893 | Associated with increased coffee consumption |
21490707 [25] | Caffeine intake: coffee drinking habits assessed Study number and race: White, n = 47341 |
| rs2472297 Allele T |
Associated with increased coffee consumption |
21357676 [26] | Caffeine intake: coffee drinking habits assessed Study number and race: mixed population, n= 6611 |
|
ADORA2A rs5751876
| |||
| rs5751876 Genotype TT |
Decreased caffeine consumption | 17616786 [14] | Caffeine intake: habitual consumption of caffeine Study number and race: Hispanic American, association found in n =2735 (full cohort), n = 1767 (nonsmoker subset), and n =968 (current smokers subset) |
| rs5751876 Genotype TT |
Increased anxiety in response to caffeine | 12825092 [27] | Caffeine intake: 150 mg caffeine administration Study number and race: mixed population, n= 100 |
| rs5751876 Genotype TT |
Increased anxiety in response to caffeine | 18305461 [28] | Caffeine intake: 150 mg caffeine administration Study number and race: mixed population, n= 102 (not significant in the European-American subset in this cohort, n= 62) |
| rs5751876 Genotype TT |
Increased anxiety in response to caffeine | 20520601 [29] | Caffeine intake: initial 100 mg caffeine administered and then 150mg 90min later, or a placebo administered at both time points (capsules) Study number and race: mixed population, n= 379 [predominantly (95%) White European] |
| rs5751876 | No increase in anxiety in response to caffeine |
22012471 [30] | Caffeine intake: 150 mg caffeine administration Study number and race: White, n=110 |
| rs5751876 Genotype CC |
Increased likelihood of being sensitive to caffeine compared with genotype TT |
17329997 [31] | Caffeine intake: questionnaire of caffeine sensitivity and sleeping habits Study number: 58 cases (self-rated caffeine sensitive), 84 controls (self-rated caffeine insensitive) (race unknown) |
| rs5751876 Genotype CC |
Increased likelihood of insomnia when exposed to caffeine |
17329997 [31] | Caffeine intake: 2 doses of 200 mg caffeine or placebo, at 11 and 23 h of wakefulness Study number and race: n =19 (race unknown) |
| rs5751876 Genotype TT and CC |
Not associated with vasodilator response | 17558310 [32] | Caffeine intake: administration of adenosine, followed by caffeine (90 mg/min/dl) for 10 min Study number and race: n= 20 (race unknown) |
|
Additional ADORA2A variants
| |||
| rs2298383 Genotype CC |
Increased anxiety in response to caffeine | 18305461 [28] | Caffeine intake: 150mg caffeine administration Study number and race: European-Americans, n=62 |
| rs4822492 Genotype CC |
Increased anxiety in response to caffeine | 18305461 [28] | Caffeine intake: 150mg caffeine administration Study number and race: European-Americans, n=62 |
| rs3761422 Genotype TT |
Increased anxiety in response to caffeine | 20520601 [29] | Caffeine intake: initial 100 mg caffeine administered and then 150mg 90min later, or a placebo administered at both time points (capsules) Study number and race: mixed population, n =379 [predominantly (95%) White European] |
| rs35320474 Genotype TT |
Increased anxiety in response to caffeine | 12825092 [27] | Caffeine intake: 150mg caffeine administration Study number and race: mixed population, n =100 |
| rs3032740 | Not associated with caffeine-related protection from Parkinson’s disease |
18759349 [16] | Caffeine intake: coffee drinking habits assessed Study number and race: mixed population, n =1100 matched case–control pairs |
| rs5751862 | Not associated with increased anxiety in response to caffeine |
20520601 [29] | Caffeine intake: initial 100 mg caffeine administered and then 150mg 90min later, or a placebo administered at both time points (capsules) Study number and race: mixed population, n =379 [predominantly (95%) White European] |
| rs5760405 | Not associated with increased anxiety in response to caffeine |
20520601 [29] | Caffeine intake: initial 100 mg caffeine administered and then 150mg 90min later, or a placebo administered at both time points (capsules) Study number and race: mixed population, n =379 [predominantly (95%) White European] |
| rs11704959 | Not associated with increased anxiety in response to caffeine |
20520601 [29] | Caffeine intake: initial 100 mg caffeine administered and then 150mg 90min later, or a placebo administered at both time points (capsules) Study number and race: mixed population, n =379 [predominantly (95%) White European] |
| rs2298383 | Not associated with increased anxiety in response to caffeine (in multiple testing) |
20520601 [29] | Caffeine intake: initial 100 mg caffeine administered and then 150mg 90min later, or a placebo administered at both time points (capsules) Study number and race: mixed population, n =379 [predominantly (95%) White European] |
| rs2267076 | Not associated with increased anxiety in response to caffeine |
20520601 [29] | Caffeine intake: initial 100 mg caffeine administered and then 150mg 90min later, or a placebo administered at both time points (capsules) Study number and race: mixed population, n =379 [predominantly (95%) White European] |
|
CYP1A1 variants
| |||
| rs4646421 | Not associated with risk of bladder cancer and coffee consumption |
18798002 [21] | Caffeine intake: coffee consumption (cups per day) Study number and race: Spanish, n= 1002 cases, n= 892 controls |
| rs2198843 | Not associated with risk of bladder cancer and coffee consumption |
18798002 [21] | Caffeine intake: coffee consumption (cups per day) Study number and race: Spanish, n= 1018 cases, n= 919 controls |
| rs2472299 | Not associated with risk of bladder cancer and coffee consumption |
18798002 [21] | Caffeine intake: coffee consumption (cups per day) Study number and race: Spanish, n= 1000 cases, n= 890 controls |
|
CYP2A6 alleles
| |||
| *4/*9 and *9/*9 | Reduced metabolite ratio of 17U/17X | 20155256 [33] | Caffeine intake: 100 mg caffeine administration Study number and race: Serbian, n= 100 |
|
CYP2E1 variants
| |||
| rs2070676 | Not associated with risk of bladder cancer and coffee consumption |
18798002 [21] | Caffeine intake: coffee consumption (cups per day) Study number and race: Spanish, n= 1018 cases, n= 918 controls |
| rs8192766 | Not associated with risk of bladder cancer and coffee consumption |
18798002 [21] | Caffeine intake: coffee consumption (cups per day) Study number and race: Spanish, n= 1017 cases, n= 919 controls |
|
AHR variants
| |||
| rs4410790 | Associated with increased coffee consumption |
21490707 [25] | Caffeine intake: coffee drinking habits assessed Study number and race: White, n=47341 |
| rs6968865 Allele T |
Associated with increased coffee consumption |
21357676 [26] | Caffeine intake: coffee drinking habits assessed Study number and race: mixed population, n =6611 |
|
GRIN2A variants
| |||
| rs4998386 Allele T |
Decreased risk of Parkinson’s disease in heavy coffee drinkers |
21876681 [34] | Caffeine intake: heavy vs. light caffeine consumption Study number and race: White, n= 1458 cases, n= 931 controls |