1-methylxanthine to theophylline

Numerator Metabolite

Structure of 1-methylxanthine
Metabolite Accession: GCST90199763
Name: 1-methylxanthine
Hmdb Id: HMDB0010738
Super Pathway: NA
Sub Pathway: NA
Inchikey: MVOYJPOZRLFTCP

Denominator Metabolite

Structure of theophylline
Metabolite Accession: GCST90199647
Name: theophylline
Hmdb Id: HMDB0001889
Super Pathway: NA
Sub Pathway: NA
Inchikey: ZFXYFBGIUFBOJW

Associated Genomic Regions

Region: rs2472297

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Clumped rQTL variant

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SNP Summary

Chr:
15
Beta (Ratio):
0.160
Position:
75027880
SE (Ratio):
0.015
Effect Allele:
T
Z-score (Ratio):
10.563
Reference Allele:
C
-log10(P):
-58.376
MAF:
0.250
Beta (Num):
0.149
Novel Locus:
No
SE (Num):
0.018
Beta (Den):
-0.011
SE (Den):
0.018
No CNV overlap
rQTL cluster:
216
Reaction Distance:
NA
Closest Genes:
CYP1A1 CYP1A2 EDC3 CSK LMAN1L

Region: rs35570672

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Clumped rQTL variant

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SNP Summary

Chr:
8
Beta (Ratio):
-0.366
Position:
18272635
SE (Ratio):
0.016
Effect Allele:
T
Z-score (Ratio):
-23.303
Reference Allele:
C
-log10(P):
-274.897
MAF:
0.223
Beta (Num):
-0.368
Novel Locus:
No
SE (Num):
0.019
Beta (Den):
-0.002
SE (Den):
0.019
No CNV overlap
rQTL cluster:
85
Reaction Distance:
NA
Closest Genes:
NAT2 PSD3 NAT1 ASAH1 PCM1

LLM Analysis

Numerator Metabolite Explanation:

Caffeine metabolism, Purine metabolism4[1], 5[2]

Denominator Metabolite Explanation:

Caffeine metabolism, Purine metabolism6[1], 7[2], 8[3]

Ratio Explanation:

This ratio reflects the metabolic activity of CYP1A2, which catalyzes the N-demethylation of theophylline to form 1-methylxanthine.1[1], 9[2], 10[3], 11[4], 12[5]

Ratio Evidence:

canonical reaction catalyzed by the enzyme

Gene Ratio Phenotype Relationship:

Genetic variation in CYP1A2 alters its xenobiotic-metabolizing activity, reflected by the ratio. This change in metabolizing procarcinogens is a plausible mechanism for the observed association with bladder cancer risk, which has a significant MR link.13[1], 14[2], 15[3] The link to gout is supported by purine metabolism.16[4], 17[5], 18[6]

Phenotype Driver:

Gene-centric:CYP1A2

Downloads

Download the full rQTL summary statistics file for this metabolite ratio. Data contains the loci listed here. For each SNP (chromosome, effect_allele, reference_allele, pos_name, position) these columns contain the summary statistics of the ratio (beta, pgain, pval, se, z), the numerator metabolite (beta_1, pval_1, n_iids_1, effect_allele_frequency_1, se_1, z_1) and the denominator metabolite (beta_2, pval_2, n_iids_2, effect_allele_frequency_2, se_2, z_2)

Download rQTL Data