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. 2010 Jun 29;11(4):317–326. doi: 10.1007/s10194-010-0230-3

STin2 VNTR polymorphism in the serotonin transporter gene and migraine: pooled and meta-analyses

Markus Schürks 1,5,✉, Pamela M Rist 1,2, Tobias Kurth 1,2,3,4
PMCID: PMC3026586  NIHMSID: NIHMS264349  PMID: 20585826

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 ~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.

Keywords: Migraine, Serotonin transporter, SLC6A4, STin2 VNTR, Meta-analysis

Full Text

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Acknowledgments

Dr. Schürks has received an investigator-initiated research grant from the Migraine Research Foundation and honoraria from L.E.K. Consulting for telephone surveys. Dr. Kurth has received investigator-initiated research funding from the French National Research Agency, the National Institutes of Health, Merck, and the Migraine Research Foundation. Further, he is a consultant to i3 Drug Safety and World Health Information Science Consultants, LLC; he has received honoraria from Genzyme, Merck, and Pfizer for educational lectures.

Conflict of interest

None.

Glossary

SLC6A4

Serotonin transporter

Bp

Base pair

STin2 VNTR polymorphism

Polymorphism consisting of a 17 bp variable number of tandem repeats in intron 2 of the SLC6A4 gene

OR

Odds ratio

CI

Confidence interval

MA

Migraine with aura

MO

Migraine without aura

IHS

International Headache Society

df

Degree of freedom

HWE

Hardy–Weinberg equilibrium

SNP

Single nucleotide polymorphism

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