Genetic variations of MTHFR gene and their association with preterm birth in Korean women.

BACKGROUND AND OBJECTIVE: The MTHFR gene encodes the methylenetetrahydrofolate reductase known to be involved in the homocysteine-methionine pathway. It has been reported that the deficiency of MTHFR activity may cause hyperhomocysteinemia which results in adverse pregnancy outcomes. Previous studies reported a correlation between the MTHFR gene polymorphisms (677 T/C and 1298 A/C) and lower MTHFR activity and its association with preterm birth in various populations. Since these results were conflicting, we analyzed the genetic association of MTHFR gene 677 T/C and 1298 A/C polymorphisms with preterm birth in Korean women. MATERIALS AND METHODS: The subjects for case-control study were collected a total of 226 Korean women (98 preterm-birth patients and 128 controls). Genotype frequency differences between the case and the control were assessed using chi-square tests. Mann-Whitney t-test was used to estimate the effects of 1298 A/C genotype on clinicopathological characteristics (systolic blood pressure, diastolic blood pressure, birth weight, and gestational age at delivery) in preterm-birth patients. RESULTS: Our results showed that the MTHFR 677 C/T polymorphism was significantly associated with preterm-birth patients in the analysis of genotype frequency (P=0.044) and the over-dominant model (OR=0.54; 95% CI, 0.320-0.920; P=0.023). The recessive model showed a marginal trend toward significance (OR=0.47; 95% CI, 0.220-1.010; P=0.046). The 1298 A/C polymorphism was also associated with reduced preterm-birth risk in the recessive model (P=0.032). In the correlation analysis, the 1298 C allele was significantly associated with increasing of gestational age at delivery in preterm-birth patients (P=0.034). CONCLUSIONS: Our findings suggested that the MTHFR gene 677 C/T and 1298 A/C polymorphisms might have protective effects for preterm birth in the Korean women.

Folate metabolizing gene polymorphisms and genetic vulnerability to preterm birth in Korean women.

BACKGROUND: The folate metabolism that converts homocysteine to methionine is closely related to the accumulation of homocysteine. Increased homocysteine levels lead to an impaired antithrombotic function of the vascular endothelium and uterine-placental circulation, resulting in abnormal pregnancy outcomes. Previous studies have reported that gene polymorphisms in folate metabolism are associated with the development of preterm birth (PTB) in various populations. OBJECTIVE: we performed a case-control study to evaluate the association between five polymorphisms in folate metabolic genes (MTHFR, MTR, MTRR, TCN2) and PTB. METHODS: In this study, a total of 254 subjects were analyzed (111 patients with PTB and 143 women at ≥ 38 weeks of gestation). Genotype and allele frequency differences between patients and control groups and the Hardy-Weinberg equilibrium were assessed using a Chi-square test. For evaluation indicators, odds ratios (ORs) of 95% confidence intervals (CI) were estimated. In addition, we analyzed the combined genotype frequencies of SNPs of folate-metabolizing genes to measure gene-gene interactions for PTB. RESULTS: Our results showed that the MTR rs1805087 GG (p = 0.031), and TCN2 rs1801198 CG genotype (OR 0.53, 95% CI 0.288-0.980, p = 0.042) were significantly associated with PTB. The MTHFR rs4846049 AA showed a marginal trend toward significance (OR 0.15, 95% CI 0.018-1.205, p = 0.041). In particular, the combined genotypes, including MTHFR rs1537514 CC-MTRR rs1801394 GG, MTHFR rs1537514 CC-TCN2 rs1801198 CG, and MTR rs1805087 AA-TCN2 rs1801198 CG, have significant interactions with PTB (OR 0.49, 95% CI 0.248-0.992, p < 0.05). CONCLUSION: The polymorphisms of folate metabolic genes may have a genetic association with the development of PTB in Korean women. A larger sample set and functional studies are required to further elucidate our findings.

Association of glutathione S-transferase M1 and T1 null/present polymorphism with physical performance in the Korean population.

Human physical performance is a highly complex phenotype that is influenced by various factors. In particular, genetic factors related to muscle fiber type, bone density, muscle performance, and metabolic processes are known to contribute in varying degrees to athlete status and physical performance in various ethnic groups. To investigate the relationship between these genetic factors and physical performances, we genotyped five genetic polymorphisms (ACE Ins/Del, ACTN3 R577X, ER-α C/T, GSTM1 null/present, and GSTT1 null/present) in 111 Korean athletes and 145 controls. We examined genotype and allele frequency differences between athletes and control groups, along with the odds ratios, using Chi square. One-way analysis of variance (ANOVA) was used to test the significance of differences in continuous variables between the multiple genetic polymorphisms and physical performance test results. The GSTM1 polymorphism exhibited a highly significant association in athletes (p = 0.017). Combined analysis of GSTM1 and GSTT1 also revealed significant differences between athletes and controls (p < 0.05). In the analysis of physical performance within athletes, the ER-α gene polymorphism was associated with the sargent jump and the side-step (p < 0.05), and the GSTM1 gene polymorphism was significantly associated with the 20 m shuttle run and sit-up (p < 0.05). Thus, our data imply that GSTM1 and ER-α gene polymorphisms were associated with physical performance in Korean athletes, although functional studies with larger sample sizes are necessary to elaborate upon these findings.

Assessment of associations between mitochondrial DNA haplogroups and attention deficit and hyperactivity disorder in Korean children.

Attention deficit hyperactivity disorder (ADHD) is a multifactorial disorder with multiple environmental and biological etiologies, including genetic factors. Until now, several genetic variants have been reported to be significantly associated with ADHD. Recently, the relationship between mitochondrial DNA (mtDNA) haplogroups and psychiatric disorders such as schizophrenia has also been reported. However, currently there are no reports pertaining to the genetic association between mtDNA haplogroups and ADHD. Therefore, we performed an mtDNA haplogroup analysis of a total of 472 Korean children (150 Children with ADHD and 322 controls). The 20 East Asian specific mtDNA haplogroups were determined using the SNaPshot assay. We also sequenced the displacement loop (D-loop) region, position 15,971-613. Our results showed that haplogroup B4 was significantly associated with ADHD (OR, 1.90; 95% CI, 1.055-3.429; p = 0.031). A marginally significant association was found in subjects with ADHD and haplogroup B5 (OR, 0.26; 95% CI, 0.059-1.139; p = 0.041). When stratified based on gender, an association was also observed between haplogroup B5 and boys diagnosed with ADHD (OR, 0.17; 95% CI, 0.022-1.340; p = 0.048). Compared with boys, girls with ADHD carried an excess of the haplogroup D4b (OR, 4.83; 95% CI, 1.352-17.272; p = 0.014). Stratified analysis of subtypes also showed significant results (combined: haplogroup B4, p = 0.007; inattentive: haplogroup F, p = 0.022). Our results showed a possible role of mtDNA haplogroups in the genetic etiology of ADHD and ADHD symptoms in Korean children.

Association of mitochondrial DNA 10398 A/G polymorphism with attention deficit and hyperactivity disorder in Korean children.

Mitochondria are subcellular organelles that contribute to aerobic ATP generation by oxidative phosphorylation (OXPHOS). Previous studies reported that mitochondrial dysfunction and deficiency caused by mitochondrial DNA polymorphisms is associated with various diseases. Especially, mitochondrial DNA 10398 A/G polymorphism is known to affect the regulation of mitochondrial calcium levels related to energy production, and its association with psychiatric disorders such as schizophrenia and bipolar disorder has been reported. However, there are no reports on the genetic relationship between mitochondrial DNA polymorphisms and ADHD. Thus, we evaluated the genetic association between 10398 A/G polymorphism and ADHD in the Korean children. Genotype frequency differences between the case and the control were assessed using Chi-square tests. Independent t-test was used to estimate the effects of genotype on Behavior Assessment System for Children (BASC-2) scales in ADHD children. Our results showed that mitochondrial DNA 10398 A/G polymorphism was significantly associated with the ADHD children (p<0.05). Stratified analyses for gender and subtypes showed a marginal trend toward significance (boys: p=0.059, and combined subtype: p=0.068, respectively). In the BASC-2 analysis, the 10398 A/G polymorphism was significantly associated with aggression behavior and leadership in ADHD boys (p<0.05). These findings suggest that the mitochondrial DNA 10398 A/G polymorphism play a possible role in the genetic etiology of ADHD in Korean children. Larger sample set and functional studies are necessary to further elucidation of our findings.