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Nitric oxide (NO), which is produced by NO synthase (NOS), plays to modulate immune function, blood vessel dilatation, neurotransmission, and mechanism of toxicity. Here, we examined whether single nucleotide polymorphisms (SNPs) of the NOS1 gene contribute to the susceptibility for overweight/obesity in Korean population. We recruited 370 subjects (159 control and 211 overweight/obese subjects), genotyped 3 SNPs in NOS1 gene using Affymetrix targeted genotyping chip array, and analyzed genetic data by Haploview4.2 and SPSS 23.0. Among 3 SNPs, 2 SNPs (rs2293048 and rs9658490) showed significant association with overweight/obesity (rs2293048, Fisher’s exact p=0.048 in codominant 2 model, Fisher’s exact p=0.045 in recessive model; rs9658490, p= 0.025, OR=1.830, 95% CI=1.078-3.105 in codominant 1, p=0.037, OR=1.734, 95% CI=1.033-2.910 in dominant model, respectively). In addition, haplotype TCG and TGG was also associated with a susceptibility of obesity (TCG, p=0.019; TGG, p=0.028). In conclusion, our study suggests that NOS1 gene may be related to overweight/obesity in Korean population.

Benign prostatic hyperplasia (BPH) is considered the most common prostate disease in elderly men. Recent studies have suggested that specific polymorphisms might be contributed to risk factors for development of BPH. The aim of present study is to investigate whether promoter single nucleotide polymorphisms (SNPs) of the NDUFA4, mitochondrial complex associated (NDUFA4) gene are risk factors for BPH in Korean men. To evaluate the associations between promoter SNPs (rs17163801, rs17163803, rs1681288, and rs3761817) of NDUFA4 gene and clinical progress of BPH, one hundred eighty one BPH patients were recruited from Department of Urology at Kyung Hee Hospital. Prostate volume, international prostate symptom score (IPSS), and prostate specific antigen (PSA) were measured. For genetic analysis, SNPStats and SPSS 22.0 were performed. Genetic models (codominant, dominant, recessive, and log-additive models) were applied to calculate the odds ratio (OR), 95% confidence interval (CI), and P value. Among tested four SNPs, three promoter SNPs (rs17163803, rs1681288, and rs3761817) showed significant associations with prostate volume after Bonferroni’s correction (rs17163803, OR=3.00, 95% CI=1.31-6.84, Pc=0.036 in codominant 1 model; rs1681288, OR=3.53, 95% CI=1.65- 7.56, Pc=0.004 in codominant 1 model; OR=2.98, 95% CI=1.47-6.05, Pc=0.0072 in dominant model; rs3761817, OR=3.86, 95% CI=1.79-8.31, Pc=0.004 in codominant 1 model; OR=3.25, 95% CI=1.59- 6.62, Pc=0.0032 in dominant model; OR=2.19, 95% CI=1.21-3.99, Pc=0.0296). The results of present study demonstrate that specific promoter polymorphisms (rs17163803, rs1681288, and rs3761817) of the NDUFA4 gene might be associated with prostate enlargement in Korean men.

Extracellular matrix (ECM) abnormality is implicated in the pathogenesis of schizophrenia. Matrix metalloproteinases (MMPs) mediate the proteolysis of ECM and may play a crucial role in neuronal plasticity. We investigated whether single nucleotide polymorphisms (SNPs) of MMP1 and MMP8 are associated with the development of schizophrenia. We also assessed the relationships between MMP1, MMP8 SNPs and the core symptoms of schizophrenia such as persecutory delusion, auditory hallucinations, affective disturbances, and poor concentration according to the Operation Criteria Checklist for Psychotic Illness (OPCRIT). Three coding SNPs (rs470558, Ala216Ala in MMP1; rs3740938, Leu291Leu and rs1940475, Lys87Glu in MMP8) were selected, and 263 patients and 283 controls were evaluated. SNPStats was used to obtain the odds ratio (OR), 95% confidence intervals (CI), and P value adjusted for age and gender as covariables. Multiple logistic regression models (codominant1, codominant2, dominant, recessive, and log-additive) were employed to analyze genetic data. As a result, the three examined SNPs were not associated with the development of schizophrenia. In the analysis of clinical symptoms, the genotype frequency of rs470558 in MMP1 was associated with auditory hallucinations (P=0.04 in the codominant1 model, P=0.014 in the dominant1 model, and P=0.0066 in the log-additive model). The allele frequency of rs470558 also showed a significant difference between schizophrenia without auditory hallucinations [the auditory hallucination (−) group] and schizophrenia with auditory hallucinations [the auditory hallucination (+) group] (P=0.009, OR= 1.94, 95% CI=1.19-3.28). The A allele frequency of rs470558 was higher in the auditory hallucination (+) group (19.2%) than that in the auditory hallucination (−) group (10.8%). Two MMP8 SNPs (rs3740938 and rs1940475) were not associated with the development and core symptoms of schizophrenia, respectively. These results suggest that the A allele of rs470558 (Ala216Ala) in MMP1 may contribute to the susceptibility to auditory hallucinations of schizophrenia.

Transforming growth factor, beta receptor II (70/80 kDa) (TGFBR2) is a tumor suppressor. Mutations in the TGFBR2 gene appear to have an increased risk of developing several cancers. To investigate whether TGFBR2 polymorphisms are associated with the development of papillary thyroid carcinoma (PTC), three single nucleotide polymorphisms (SNPs) of TGFBR2 (rs764522, -1444C/G; rs3087465, -834G/A; rs2228048, Asn389Asn) were selected and genotyped by direct sequencing in 92 PTC patients and 330 control subjects. We also assessed the relationships between three SNPs of TGFBR2 and clinicopathologic characteristics of PTC such as size ( 1 cm), number (unifocality and multifocality), location (one lobe and both lobe), extrathyroidal invasion, and lymph node metastasis. SNPStats and Haploview version 4.2 were used to analyze genetic data. Multiple logistic regression models (codominant1, codominant2, dominant, recessive, overdominant, and log-additive) were performed to calculate odds ratios (ORs), 95% confidence intervals (CIs), and P values. The three examined SNPs were not associated with PTC. In clinicopathologic characteristics, two promoter SNPs (rs3087465 and rs764522) were associated with lymph node metastasis (rs3087465, P=0.009 in the codominant1 model, P=0.043 in the dominant model, P= 0.003 in the overdominant model; rs764522, P=0.021 in the codominant1 model, P=0.044 in the dominant model, P=0.016 in the overdominant model). The synonymous SNP rs2228048 was associated with extrathyroidal invasion (P=0.024 in the dominant model, P=0.015 in the log-additive model). The allele frequency of rs2228048 was significantly different between PTC with extrathyroidal invasion and PTC without extrathyroidal invasion (P=0.018, OR=0.46, 95% CI=0.24–0.88). These results suggest that TGFBR2 may be associated with the progression of PTC in Korean population.

Abnormal neurodevelopmental processes are found in the brains of schizophrenia patients. Nerve growth factor (beta polypeptide) (NGF) is known to play a major role in neuronal growth, differentiation, and neuroprotection of the brain. To investigate whether NGF polymorphisms are associated with schizophrenia patients, eight single nucleotide polymorphisms (SNPs; rs10776800, rs11102924, rs4839435, rs12760036, rs11102919, rs11466098, rs2268793, and rs6330) of the NGF were selected and genotyped by direct sequencing in 217 schizophrenia patients and 378 control subjects. SNPAnalyzer, SNPStats, and Haploview version 4.2 were used to analyze the genetic data. Multiple logistic regression models (codominant1, codominant2, dominant, recessive, overdominant, and log-additive) were performed to calculate odds ratios (ORs), 95% confidence intervals (CIs), and P values. P values (P c ) were recalculated using Bonferroni correction to better define results. It was found that the allele frequency of rs12760036 SNP of the NGF was associated with the susceptibility to schizophrenia (P c =0.0016, OR=1.65, 95% CI=1.27–2.15). Genotype frequency of rs12760036 of the NGF was also associated with schizophrenia patients (P c =0.0024, OR= 1.90, 95% CI=1.34–2.71). In the linkage disequilibrium block between rs12760036 and rs4839435, the AG and CA haplotype frequencies between schizophrenia patients and the control group were significantly different (P=0.0002; P=0.0033, respectively). These results suggest that the rs12760036 may be a risk factor to the susceptibility of schizophrenia in Korean population.

Glutamate toxicity plays a key role in neuronal cell death. The aim of this study was to investigate whether three single nucleotide polymorphisms (SNPs) (rs2073287, intron; rs2942, Lys931Lys; rs6923492, Ser993Pro) of glutamate receptor, metabotropic 1 (GRM1) were associated with the development and clinical features of stroke. We recruited 365 control subjects and 195 stroke patients consisted of 119 ischemic stroke (IS) and 76 intracerebral hemorrhage (ICH). All stroke patients were divided into clinical subgroups according to the scores of the National Institutes of Health Stroke Survey (NIHSS, < 6 and ≥ 6) and Modified Barthel Index (MBI, < 60 and ≥60). SNPStats and SPSS 18.0 were conducted to evaluate odds ratios (ORs), 95% confidence intervals (CIs), and P values. Multiple logistic regression models were performed to analyze the genetic data. A rs2073287 SNP of GRM1 was associated with the susceptibility of stroke (IS+ ICH) (P=0.002, OR=1.49, 95% CI=1.16-1.92 in allele frequencies). The rs2073287 was also associated with the development of IS (P=0.028, OR=1.40, 95% CI= 1.04-1.89 in allele frequencies) and ICH (P=0.006, OR=1.65, 95% CI=1.16–2.35 in allele frequencies). The G allele frequencies of rs2073287 in stroke (IS+ ICH), IS, and ICH were higher than in the control group, respectively. The rs2942 and rs6923492 were not related to stroke (IS+ICH), IS, and ICH, respectively. These results suggested that the G allele of rs2073287 could be a risk factor to the susceptibility of stroke in Korean population.

Cholesterol homeostasis is essential for functional integrity of lipid. Niemann-Pick disease, type C2 (NPC2) encodes a protein containing a lipid recognition domain. NPC2 is related to regulation of cholesterol and other lipids. To evaluate NPC2 gene and its correlation to obesity in Korean population, 214 overweight/obese and 160 healthy control subjects were enrolled in this study. Genomic DNA was extracted from peripheral blood. Two tag single nucleotide polymorphisms (tag SNPs) in NPC2 gene were selected (rs8008540 and rs917394). Genotypes were determined using direct sequencing. For the analysis of genetic data, Helixtree software, SNPAnalyzer, SNPStats, and Haploview version 4.2 were used. Multiple logistic regression models (codominant, dominant, and recessive models) were performed for odds ratio (OR), 95% confidence interval (CI), and P value. In allele distribution analysis, allele of rs917394 was associated with obesity (OR=1.45, 95% CI=1.08–1.95, P=0.014). The genotype distributions of tag SNPs (rs8008540 and rs917394) were showed significant differences between overweight/obese and control subjects [rs8008540, OR=1.63, 95% CI=1.04–2.58, P=0.034 in codominant 1 (C/C versus C/T) model, OR=1.58, 95% CI=1.03–2.44, P=0.036 in dominant model; rs917394, OR=2.33, 95% CI=1.20–4.52, P= 0.013 in codominant model 2 (T/T versus C/C), OR= 1.62, 95% CI=1.05–2.52, P=0.030 in dominant model]. Haplotype (CT) was also associated with overweight/obese (frequency=0.589, chi square=6.100, P=0.014). These results indicate that NPC2 gene may be associated with obesity in Korean population.