Abstract
Although both methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms have been associated with type 2 diabetes (T2D), their interactions with being overweight/obesity on T2D risk remain unclear. To evaluate the associations of the two polymorphisms with T2D and their interactions with being overweight/obesity on T2D risk, a case-control study of 180 T2D patients and 350 healthy controls was conducted in northern China. Additive interaction was estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (S). After adjustments for age and gender, borderline significant associations of the MTHFR C677T and MTRR A66G polymorphisms with T2D were observed under recessive (OR = 1.43, 95% CI: 0.98–2.10) and dominant (OR = 1.43, 95% CI: 1.00–2.06) models, respectively. There was a significant interaction between the MTHFR 677TT genotype and being overweight/obesity on T2D risk (AP = 0.404, 95% CI: 0.047–0.761), in addition to the MTRR 66AG/GG genotypes (RERI = 1.703, 95% CI: 0.401–3.004; AP = 0.528, 95% CI: 0.223–0.834). Our findings suggest that individuals with the MTHFR 677TT or MTRR 66AG/GG genotypes are more susceptible to the detrimental effect of being overweight/obesity on T2D. Further large-scale studies are still needed to confirm our findings.
Highlights
About 415 million people were estimated to have diabetes in 2015, and the number is still rising in almost all countries, according to the International Diabetes Federation [1]
We explored the additive interaction between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and being overweight/obesity under the recessive model (Table 3)
We performed power calculations and the results indicated that the power of additive interaction analysis between the MTHFR C677T and MTRR A66G polymorphisms with being overweight/obesity on type 2 diabetes (T2D) risk were 42.7% and 75.3%, respectively
Summary
About 415 million people were estimated to have diabetes in 2015, and the number is still rising in almost all countries, according to the International Diabetes Federation [1]. China has the largest number of diabetic patients in the world and has seen this growing trend [1,2,3]. Type 2 diabetes (T2D) is the most common type of diabetes. Its etiology is complicated because this disease involves multiple genetic and environmental factors and their interactions [4]. Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) have been suggested as candidate genes for studying the association with T2D [5,6,7]. Res. Public Health 2016, 13, 1243; doi:10.3390/ijerph13121243 www.mdpi.com/journal/ijerph
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