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OCT1, SERT Genes Play Role in Metformin Intolerance

Intolerance up with low-expressing SERT S* alleles; multiplicative interaction for OCT1, SERT genotypes

genetic helix

MONDAY, Aug. 15, 2016 (HealthDay News) -- The interaction between the organic cation transporter 1 (OCT1) and the serotonin reuptake transporter (SERT) seems to play a role in metformin intolerance, according to a study published online Aug. 4 in Diabetes Care.

Tanja Dujic, Ph.D., from the University of Sarajevo in Bosnia and Herzegovina, and colleagues examined the correlation between a common polymorphism in the SERT gene and metformin gastrointestinal intolerance. The effect of composite SERT 5-HTTLPR/rs25531 genotypes L*L*, L*S*, and S*S* was explored in 1,356 fully-tolerant and 164 extreme metformin-intolerant patients.

The researchers found that the odds of metformin intolerance were increased with the number of low-expressing SERT S* alleles (odds ratio, 1.31). There was a multiplicative interaction between OCT1 and SERT genotypes (P = 0.003). In patients carrying L*L* genotype, the presence of two deficient OCT1 alleles correlated with more than nine-fold increased odds of metformin intolerance in analyses stratified by SERT genotype (odds ratio, 9.25); a much smaller effect was seen in L*S* carriers and no effect was seen in S*S* carriers.

"Further studies are needed to replicate these findings and to substantiate the hypothesis that metformin gastrointestinal side effects could be related to the reduced intestinal serotonin uptake," the authors write.

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