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Enrichment of MTHFR 677?T in a Chinese long-lived cohort and its association with lipid modulation.

ABSTRACT: BACKGROUND: Variants in the Methylenetetrahydrofolate reductase (MTHFR) gene may result in a lowered catalytic activity and associate with subsequent elevated serum homocysteine (Hcy) concentration, abnormal DNA synthesis and methylation, cardiovascular risk, and unhealthy aging. Several investigations on the relationship of MTHFR C677T polymorphism with serum lipid profile and longevity have been conducted in some populations, but the findings remain mixed. Herein, we sought to look at the association between MTHFR C677T and lipid profile in a longevous cohort in Bama, a well-known home of longevity in China. METHODS: Genotyping of MTHFR C677T was undertaken in 516 long-lived inhabitants (aged 90 and older, long-lived group, LG) and 493 healthy controls (aged 60-75, non-long-lived group, non-LG) recruited from Bama area. Correlation between MTHFR genotypes and lipids was then evaluated. RESULTS: T allele and TT genotype were significantly more prevalent in LG (P=0.001 and 0.002, respectively), especially in females, than in non-LG. No difference in the tested lipid measures among MTHFR C677T genotypes was observed in LG, non-LG and total population (P>0.05 for all). However, female but not male T carriers exhibited higher TC and LDL-C levels than did T noncarriers in the total population and in LG after stratification by sex (P<0.05 for each). These differences did not however remain through further subdivision by hyperlipidemia and normolipidemia. CONCLUSION: The higher prevalence of MTHFR 677?T genotypes and its modest unfavorable impact on lipids in Bama long-lived individuals may imply an existence of other protective genotypes which require further determination.

SUBMITTER: Chen NY

PROVIDER: S-EPMC4092207 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Enrichment of MTHFR 677 T in a Chinese long-lived cohort and its association with lipid modulation.

Chen Ning-Yuan NY Liu Cheng-Wu CW Du Li-Li LL Xiao Li-Ping LP Ge Lin L Wang Yi-Yuan YY Wei Zhen Z Wu Hua-Yu HY Luo Chen-Yuan CY Liang Liang L Peng Jun-Hua JH Luo Xiao-Qiu XQ Yin Rui-Xing RX Nguyen Cuc Phuong CP Pan Shang-Ling SL

Lipids in health and disease 20140626

<h4>Background</h4>Variants in the Methylenetetrahydrofolate reductase (MTHFR) gene may result in a lowered catalytic activity and associate with subsequent elevated serum homocysteine (Hcy) concentration, abnormal DNA synthesis and methylation, cardiovascular risk, and unhealthy aging. Several investigations on the relationship of MTHFR C677T polymorphism with serum lipid profile and longevity have been conducted in some populations, but the findings remain mixed. Herein, we sought to look at t ...[more]

PMID: 24968810

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Project description:BackgroundAssociation between rectal or colon cancer risk and serine hydroxymethyltransferase 1 (SHMT1) C1420T or methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms was assessed. The serum total homocysteine (HCY), marker of folate metabolism was also investigated.MethodsThe SHMT1 and MTHFR genotypes were determined by real-time PCR and PCR-RFLP, respectively in 476 patients with rectal, 479 patients with colon cancer and in 461 and 478, respective controls matched for age and sex. Homocysteine levels were determined by HPLC kit. The association between polymorphisms and cancer risk was evaluated by logistic regression analysis adjusted for age, sex and body mass index. The population stratification bias was also estimated.ResultsThere was no association of genotypes or diplotypes with colon cancer. The rectal cancer risk was significantly lower for SHMT1 TT (OR = 0.57, 95% confidence interval (CI) 0.36-0.89) and higher for MTHFR CT genotypes (OR = 1.4, 95%CI 1.06-1.84). A gene-dosage effect was observed for SHMT1 with progressively decreasing risk with increasing number of T allele (p = 0.014). The stratified analysis according to age and sex revealed that the association is mainly present in the younger (< 60 years) or male subgroup. As expected from genotype analysis, the SHMT1 T allele/MTHFR CC diplotype was associated with reduced rectal cancer risk (OR 0.56, 95%CI 0.42-0.77 vs all other diplotypes together). The above results are unlikely to suffer from population stratification bias. In controls HCY was influenced by SHMT1 polymorphism, while in patients it was affected only by Dukes' stage. In patients with Dukes' stage C or D HCY can be considered as a tumor marker only in case of SHMT1 1420CC genotypes.ConclusionsA protective effect of SHMT1 1420T allele or SHMT1 1420 T allele/MTHFR 677 CC diplotype against rectal but not colon cancer risk was demonstrated. The presence of SHMT1 1420 T allele significantly increases the HCY levels in controls but not in patients. Homocysteine could be considered as a tumor marker in SHMT1 1420 wild-type (CC) CRC patients in Dukes' stage C and D. Further studies need to clarify why SHMT1 and MTHFR polymorphisms are associated only with rectal and not colon cancer risk.

Dataset Information

Enrichment of MTHFR 677?T in a Chinese long-lived cohort and its association with lipid modulation.

Publications

Enrichment of MTHFR 677 T in a Chinese long-lived cohort and its association with lipid modulation.

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