Article

No Influence of 5-HTTLPR Gene Polymorphism on Migraine Symptomatology, Comorbid Depression, and Chronification

Neurologie, Krankenhaus Göttlicher Heiland, Vienna, Austria.
Headache The Journal of Head and Face Pain (Impact Factor: 3.19). 05/2009; 50(3):420-30. DOI: 10.1111/j.1526-4610.2009.01428.x
Source: PubMed

ABSTRACT The serotonergic system is thought to play an important role for mediating susceptibility to migraine and depression, which is frequently found comorbid in migraine. The functional polymorphism in the serotonin transporter gene linked polymorphic region (5-HTTLPR/SLC6A4) was previously associated with attack frequency and, thus, possibly with chronification.
We hypothesized that patients with the "s" allele have higher attack frequency and, paralleling results in depression research, higher scores of depression.
Genetic analysis of the SLC6A4 44 bp insertion/deletion polymorphism (5-HTTLPR) was performed in 293 patients with migraine with and without aura. Self-rating questionnaires were used for assessment of depression.
Multinomial logistic regression analysis found no evidence for association of the 5-HTTLPR polymorphism with either depression or migraine attack frequency.
We were not able to demonstrate any influence of the serotonin transporter 5-HTTLPR polymorphism on migraine phenomenology (attack frequency or comorbid depression), thereby excluding this variant to be a common genetic denominator for chronic migraine and depression.

Download full-text

Full-text

Available from: Dorothea Koenig, Aug 01, 2015
0 Followers
 · 
212 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Data on the association between the SLC6A4 STin2 VNTR polymorphism and migraine are conflicting. To perform pooled and meta-analyses, we searched for studies published until September 2009 using electronic databases (MEDLINE, EMBASE, Science Citation Index) and reference lists of studies. Assessment for eligibility and extraction of data was performed by two independent investigators. We extracted allele and genotype frequencies for each study. We then calculated study-specific and pooled odds ratios (OR) and 95% confidence intervals (CI) assuming allele and genotype models. We also calculated pooled ORs and 95% CIs based on study-specific effect estimates for the allele model. We included five studies investigating the association between the STin2 VNTR polymorphism and migraine. Results from the allele model suggested a protective effect against migraine for the STin2.9 and STin2.10 alleles compared to the STin2.12 allele among populations of European descent, which however was not significant. Results from the genotype model indicated a significant approximately 25% reduced risk for migraine among carriers of the 10/12 genotype compared with carriers of the 12/12 genotype among all study populations (OR = 0.76, 95% CI 0.60-0.97) for any migraine, which was more pronounced among populations of European descent (OR = 0.68, 95% CI 0.53-0.87). Results for migraine with and without aura were of similar magnitude, but were not statistically significant. Our results suggest a protective effect of non-STin2.12 alleles compared to STin2.12 alleles, respectively, 10/12 and 10/10 genotypes compared to the 12/12 genotype against migraine among populations of European descent. Associations in non-European populations may differ.
    The Journal of Headache and Pain 08/2010; 11(4):317-26. DOI:10.1007/s10194-010-0230-3 · 3.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of the present observational study was to assess the value of the C825T polymorphism of the beta-3 subunit of G proteins (GNB3) as well as of variants in the SLC6A4 gene (5HTTLPR and STin2 VNTR) and DRD2 gene (TaqI A and NcoI) as predictive markers for consistency in headache response to triptans in migraine patients. Consistent responders to triptans were defined as the migraineurs who experienced a > or =2 point reduction in a 4-point scale intensity of pain from 3 (severe) to 0 (absent) 2h after triptan administration, in at least two attacks out of the three. Genotyping was performed by PCR and PCR-RFLP on genomic DNA extracted from peripheral blood. The impact of clinical and biological variables on consistency status of headache response to triptans was evaluated by using a binary logistic regression model with stepwise selection. Forty-three (33%) of the 130 migraine patients included in the study did not consistently respond to triptan administration. In a binary logistic regression model, STin 2.12/12 genotype (OR=3.363, 95% CI: 1.262-8.966, P=0.005) and non-use of migraine prophylactic medications (OR=2.848, 95% CI: 1.019-7.959, P=0.010) were found as significant factors increasing the odds of achieving inconsistent response to triptans. The analysis of classificatory power of the model showed moderate values of sensitivity (0.56), high specificity (0.87), and an overall prediction correctness (0.77). These results support the role of STin2 VNTR polymorphism of serotonin transporter gene as a relevant genetic factor conferring a higher risk of inconsistent response to triptans in migraine patients.
    European journal of pharmacology 09/2010; 641(2-3):82-7. DOI:10.1016/j.ejphar.2010.04.049 · 2.68 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Data on the association between the SLC6A4 5-HTTLPR polymorphism and migraine are conflicting. We performed a systematic review and meta-analysis among studies published up to September 2009. For each study with genotype information, we calculated odds ratios (OR) and 95% confidence intervals (CI) assuming additive, dominant, and recessive genetic models. We then calculated pooled ORs and 95% CIs. Among the ten studies identified there was no overall association between the polymorphism and any migraine for Europeans or Asians. However, European women carrying the S allele had an increased risk for any migraine (dominant model: pooled OR=2.02; 95% CI 1.24-3.28). Results among Europeans further suggested an increased risk for migraine with aura among carriers of the S/S genotype (recessive model: pooled OR=1.41; 95% CI 0.83-2.40). While our results indicate no overall association between the SLC6A4 5-HTTLPR polymorphism and migraine among Europeans and Asians, gender and migraine aura status may have modifying roles among Europeans.
    Cephalalgia 11/2010; 30(11):1296-305. DOI:10.1177/0333102410362929 · 4.12 Impact Factor
Show more