Supplementary Material
Association of TH01 with human longevity revisited
Nicole von Wurmb-Schwark1, Amke Caliebe2, Thorsten Schwark1, Rabea Kleindorp3,
Micaela Poetsch4, Stefan Schreiber3,5, Almut Nebel3*
1
Institute of Legal Medicine, 2Institute of Medical Informatics and Statistics, 3Institute of
Clinical Molecular Biology, 5Popgen Biobank, all at the Christian-Albrechts-University and
the University Hospital Schleswig-Holstein, Kiel, Germany, 4Institute of Legal Medicine,
University Hospital Essen, Germany
1
Investigation of a possible association between variation in TH01 STR alleles and
arterial hypertension or smoking
In an exploratory analysis, we investigated a possible association of TH01 STR alleles with
arterial hypertension and smoking. Earlier studies reported inconsistent results1-6. Here, we
compared the overall frequency distribution between the groups ever smokers and never
smokers as well as between individuals with and without high blood pressure. Furthermore,
we ascertained for each phenotype the frequency of the previously described candidate alleles
(for high blood pressure: alleles 9.3 and 101, for smoking alleles 7 and 94-6) in LLI and
controls, respectively, and tested for carrier or additive effect. All comparisons were
performed in the entire sample and subgroups stratified by sex and age (LLI and controls),
using Fisher’s exact test.
For high blood pressure, in female LLI patients the allele 9.3 showed a nominally significant
increase for carriership (p=0.046, Supplementary Table 1). This increase was not observed in
male LLI, in controls or the whole sample or when an additive risk model was considered.
There was no difference for allele 10 in individuals with and without high blood pressure
(Supplementary Table 1). For smoking, allele 7 revealed a nominally significant increase in
LLI smokers for carriership (p=0.034, Supplementary Table 2). This increase was not
observed in controls or the whole sample or when an additive risk model was considered.
Allele 9 showed no difference in smokers versus non-smokers (Supplementary Table 2).
The nominally borderline-significant results represent interesting, yet tentative, results as they
were obtained from an explorative analysis and were not adjusted for multiple testing.
2
Moreover, these were only obtained in subgroups and not robust and our study was not
designed to investigate arterial hypertension and smoking. The possible associations between
THO1 allele variation and arterial hypertension or smoking warrant further studies that
provide larger sample sizes and are specially designed for this purpose.
3
Supplementary Table 1: THO1 allele frequencies in individuals with and without
hypertension
5
6
7
8
9
9.3
10
with hypertension
(n=319)
absolute
relative
frequency frequency
1
0.0016
139
0.22
114
0.18
57
0.089
105
0.16
216
0.34
6
0.0094
without hypertension
(n=550)
absolute
relative
frequency
frequency
3
0.0027
233
0.21
179
0.16
121
0.11
180
0.16
374
0.34
10
0.0091
p value
pCCA=0.87
p9.3,LLI=0.074
p9.3,LLI,f=0.046
p9.3,LLI,m=0.76
p9.3,contr=0.25
p10,LLI=0.50
p10,contr=1.00
pCCA: p value for overall allele frequency comparison of individuals with or without
hypertension
p9.3,LLI: p value for comparison of allele 9.3 carriership of individuals with or without
hypertension in all LLI
p9.3,LLI,f: p value for comparison of allele 9.3 carriership of individuals with or without
hypertension in female LLI
p9.3,LLI,m: p value for comparison of allele 9.3 carriership of individuals with or without
hypertension in male LLI
p9.3,contr: p value for comparison of allele 9.3 carriership of individuals with or without
hypertension in controls
p10,LLI: p value for comparison of allele 10 carriership of individuals with or without
hypertension in LLI
p10,contr: p value for comparison of allele 10 carriership of individuals hypertension in controls
4
Supplementary Table 2: THO1 allele frequencies in smokers and non-smokers
5
6
7
8
9
9.3
10
smokers (n=406)
abs.
rel.
frequency frequency
2
0.0025
175
0.22
150
0.18
71
0.17
136
0.087
270
0.33
8
0.0099
non-smokers (n=470)
abs.
rel.
frequency frequency
2
0.0021
207
0.22
147
0.16
103
0.11
149
0.16
324
0.34
8
0.0085
p values
pCCA =0.56
p7,LLI=0.034
p7,contr=1.00
p9,LLI=0.74
p9,contr=0.69
pCCA: p value for overall allele frequency comparison of smokers and non-smokers
p7,LLI: p value for comparison of allele 7 carriership of smokers and non-smokers in LLI
p7,contr: p value for comparison of allele 7 carriership of smokers and non-smokers in controls
p9,LLI: p value for comparison of allele 9 carriership of smokers and non-smokers in LLI
p9,contr: p value for comparison of allele 9 carriership of smokers and non-smokers in controls
5
References
1
2
3
4
5
6
Sharma P, Hingorani A, Jia H et al: Positive association of tyrosine hydroxylase microsatellite
marker to essential hypertension. Hypertension 1998; 32: 676-682.
Klintschar M, Immel UD, Stiller D, Kleiber M: TH01, a tetrameric short tandem repeat locus
in the tyrosine hydroxylase gene: association with myocardial hypertrophy and death from
myocardial infarction? Dis Markers 2005; 21: 9-13.
Lerman C, Shields PG, Main D et al: Lack of association of tyrosine hydroxylase genetic
polymorphism with cigarette smoking. Pharmacogenetics 1997; 7: 521-524.
Anney RJ, Olsson CA, Lotfi-Miri M, Patton GC, Williamson R: Nicotine dependence in a
prospective population-based study of adolescents: the protective role of a functional tyrosine
hydroxylase polymorphism. Pharmacogenetics 2004; 14: 73-81.
Olsson C, Anney R, Forrest S et al: Association between dependent smoking and a
polymorphism in the tyrosine hydroxylase gene in a prospective population-based study of
adolescent health. Behav Genet 2004; 34: 85-91.
Rodriguez S, Huang S, Chen XH et al: A study of TH01 and IGF2-INS-TH haplotypes in
relation to smoking initiation in three independent surveys. Pharmacogenet Genomics 2006;
16: 15-23.
6