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      Interaction of MTHFR C677T polymorphism with smoking in susceptibility to diabetic nephropathy in Chinese men with type 2 diabetes

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          Abstract

          We investigated the interaction of MTHFR C677T polymorphism (rs1801133) with smoking in susceptibility to diabetic nephropathy (DN) in Chinese men with type 2 diabetes mellitus (T2DM). We studied 655 Chinese men with T2DM, who were divided into two groups (321 with DN and 334 without DN). The genotype of MTHFR C677T polymorphism was detected by real-time polymerase chain reaction. MTHFR TT genotype carried a higher risk of DN compared with the CC genotype (OR = 2.05; P = 0.002). The T allele showed marked association with DN development in patients who smoked, using additive, recessive, and dominant models (OR = 1.60, 1.83, and 1.88, respectively; P = 0.006, 0.002, and 0.04, respectively), which was not observed in the nonsmoking group. Patients with TT and CT genotypes, who smoked had a higher risk of DN compared with the control group (non-smoking with CC genotype; OR = 3.73 and 2.28, respectively; P < 0.001 and P = 0.004, respectively), whereas the other groups were not observed. In conclusion, the T allele of rs1801133 may be a risk factor for DN in Chinese men with T2DM, and synergy appears to exist between the MTHFR rs1801133 and smoking in susceptibility to DN.

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          Gene-environment interplay and psychopathology: multiple varieties but real effects.

          Gene-environment interplay is a general term that covers several divergent concepts with different meanings and different implications. In this review, we evaluate research evidence on four varieties of gene-environment interplay. First, we consider epigenetic mechanisms by which environmental influences alter the effects of genes. Second, we focus on variations in heritability according to environmental circumstances. Third, we discuss what is known about gene-environment correlations. Finally, we assess concepts and findings on the interaction between specific identified genes and specific measured environmental risks. In order to provide an understanding of what may be involved in gene-environment interplay, we begin our presentation with a brief historical review of prevailing views about the role of genetic and environmental factors in the causation of mental disorders, and we provide a simplified account of some of the key features of how genes 'work'.
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            Tobacco smoke is a source of toxic reactive glycation products.

            Smokers have a significantly higher risk for developing coronary and cerebrovascular disease than nonsmokers. Advanced glycation end products (AGEs) are reactive, cross-linking moieties that form from the reaction of reducing sugars and the amino groups of proteins, lipids, and nucleic acids. AGEs circulate in high concentrations in the plasma of patients with diabetes or renal insufficiency and have been linked to the accelerated vasculopathy seen in patients with these diseases. Because the curing of tobacco takes place under conditions that could lead to the formation of glycation products, we examined whether tobacco and tobacco smoke could generate these reactive species that would increase AGE formation in vivo. Our findings show that reactive glycation products are present in aqueous extracts of tobacco and in tobacco smoke in a form that can rapidly react with proteins to form AGEs. This reaction can be inhibited by aminoguanidine, a known inhibitor of AGE formation. We have named these glycation products "glycotoxins." Like other known reducing sugars and reactive glycation products, glycotoxins form smoke, react with protein, exhibit a specific fluorescence when cross-linked to proteins, and are mutagenic. Glycotoxins are transferred to the serum proteins of human smokers. AGE-apolipoprotein B and serum AGE levels in cigarette smokers were significantly higher than those in nonsmokers. These results suggest that increased glycotoxin exposure may contribute to the increased incidence of atherosclerosis and high prevalence of cancer in smokers.
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              Geographical and ethnic variation of the 677C>T allele of 5,10 methylenetetrahydrofolate reductase (MTHFR): findings from over 7000 newborns from 16 areas world wide.

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                Author and article information

                Contributors
                caoyongtong92@sina.com
                lp8675@163.com
                Journal
                J Hum Genet
                J. Hum. Genet
                Journal of Human Genetics
                Springer Singapore (Singapore )
                1434-5161
                1435-232X
                5 November 2018
                5 November 2018
                2019
                : 64
                : 1
                : 23-28
                Affiliations
                [1 ]ISNI 0000 0004 1771 3349, GRID grid.415954.8, Clinical Laboratory, , China-Japan Friendship Hospital, ; Beijing, China
                [2 ]ISNI 0000 0004 1771 3349, GRID grid.415954.8, Department of Endocrinology, , China-Japan Friendship Hospital, ; Beijing, China
                [3 ]ISNI 0000 0004 1771 3349, GRID grid.415954.8, Beijing Key Laboratory of Immune-Mediated Inflammatory Diseases, , Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, ; Beijing, China
                Article
                531
                10.1038/s10038-018-0531-y
                6342826
                30397262
                7720e630-feb1-4117-9ce2-6184830166de
                © The Author(s) under exclusive licence to The Japan Society of Human Genetics 2018
                History
                : 3 July 2018
                : 2 September 2018
                : 17 October 2018
                Funding
                Funded by: This study was supported by the the National Natural Science Foundation of China (Grant no: 81703892, 81503418).
                Categories
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                Custom metadata
                © The Japan Society of Human Genetics 2019

                Genetics
                Genetics

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