Ling Zhang

Publications (10)27.87 Total impact

• Article: Association of the cell death-inducing DNA fragmentation factor alpha-like effector A (CIDEA) gene V115F (G/T) polymorphism with phenotypes of metabolic syndrome in a Chinese population.

  Ling Zhang, Ying Dai, Lili Bian, Wei Wang, Masaaki Muramatsu, Qi Hua
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  ABSTRACT: The CIDEA gene is involved in energy metabolism and a non-synonymous single nucleotide polymorphism (SNP), V115F (G/T), is a risk factor for obesity in Swedish subjects and metabolic syndrome (MetS) in Japanese subjects. However, the risk allele was a G in Swedish subjects and a T in Japanese subjects. The present study investigated the association between this SNP and MetS in a Chinese population. Three hundred and fifty-one subjects evaluated at the Cardiac Clinic in Xuanwu Hospital for MetS risks were recruited. Anthropometric measurements, blood pressure, fasting blood glucose, and blood lipid levels were determined in addition to the polymorphism. The proportion of subjects with MetS was significantly higher based on genotype, in the order: GG<GT<TT (p=0.003). In multiple logistic regression analysis, the odds ratios for MetS in the GT and TT genotypes, compared to the referent GG genotype, were 2.26 (p=0.003) and 2.89 (p=0.002), respectively. Similar trends were observed for the related phenotypes of central obesity (GT: OR=2.20, p=0.004; TT: OR=3.31, p=0.002) and dyslipidemia (GT: OR=1.73, p=0.047; TT: OR=2.10, p=0.03). The T allele of the CIDEA V115F SNP is a risk factor for MetS and its related phenotypes in a Chinese population.
  Diabetes research and clinical practice 11/2010; 91(2):233-8. · 2.16 Impact Factor
• Article: Increasing the number of SNP loci does not necessarily improve prediction power at least in the comparison of MTHFR SNP and haplotypes.

  Koichi Miyaki, Yoshimitsu Takahashi, Yixuan Song, Ling Zhang, Masaaki Muramatsu, Takeo Nakayama
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  ABSTRACT: Rapid advances in genotyping technology have made it possible to easily utilize a large number of genetic markers. According to information theory, an increase in the number of markers provides more information; however, the clinical usefulness does not increase linearly. This study aimed to assess the effect of folic acid supplementation quantitatively in MTHFR haplotypes, and compare its prediction power with that of the C677T single nucleotide polymorphism (SNP) alone. The study was a randomized, double-blind, placebo-controlled trial, designed in accordance with the CONSORT statement. The participants were 202 healthy Japanese males who were administered either folic acid at 1 mg/day or a placebo postoperatively for 3 months. The primary endpoint was the total plasma homocysteine levels (tHcy). Stratified analysis by HapMap-based tag SNPs was performed. Of 52 SNPs on the MTHFR gene, 4 SNP loci covering more than 80% of the information were selected, and the haplotypes were estimated. The haplotypes were classified into 3 groups (Hap0, Hap1, and Hap2), on the basis of the number of times the most frequent haplotype was present. The greatest decrease was observed in Hap2 (6.61 micromol/L), compared with the other haplotypes (Hap0, 2.67; Hap1, 2.60) (trend test, P < 0.01). The haplotype information obtained was not more informative than that obtained with grouping by a single SNP, C677T, which strongly influences enzyme activity. Grouping by the C677T SNP alone was almost as good a predictor of the homocysteine-lowering effects as was grouping by the 4 best SNPs. This shows that increasing the number of typed SNPs does not necessarily provide more information, at least for this gene. A more efficient, cost-informative method for analyzing genomic data is required.
  Journal of Epidemiology 12/2008; 18(6):243-50. · 1.86 Impact Factor
• Article: Pharmacogenetics of hormone replacement therapy for climacteric symptoms.

  Chikari Takeo, Kanako Ugai, Jungo Araki, Ling Zhang, Masanori Baba, Wataru Ohashi, Koichi Ueno, Yoichi Suzuki, Keiko Amano, Aizan Hirai, Masaaki Muramatsu
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  ABSTRACT: Hormone replacement therapy (HRT) is highly effective for women suffering from climacteric symptoms, with occasionally severe side effects. To determine which women needs HRT for climacteric symptoms indeed, pharmacogenetical approach for HRT was performed. Under the condition of minimal HRT, 33 patients required HRT for more than 1 year and the remaining 156 did not. Three single nucleotide polymorphisms (SNPs) in estrogen receptor alpha (ERalpha) gene and 3 SNPs and a microsatellite polymorphism in estrogen receptor beta (ERbeta) gene were analyzed using LightTyper and PCR. Homozygous for 18 CA repeats of D14S1026 (OR 8.00, 95% CI 2.56-25.02, P<0.001) and rs1256049 (OR 6.35, 95% CI 2.38-16.92, P=0.004) in ERbeta associated with minimal HRT. In contrast, rs1271572 in 789bp upstream region of ERbeta (OR 0.30, 95% CI 0.14-0.65, P=0.002) gene decreased HRT. rs2228480 in ERalpha gene also increased HRT. Tailored decisions can be expected on the future use of HRT referring genetic polymorphisms of individuals.
  Biochemical and Biophysical Research Communications 10/2008; 374(4):604-8. · 2.48 Impact Factor
• Article: Cell death-inducing DNA fragmentation factor alpha-like effector A (CIDEA) gene V115F (G-->T) polymorphism is associated with phenotypes of metabolic syndrome in Japanese men.

  Ling Zhang, Koichi Miyaki, Takeo Nakayama, Masaaki Muramatsu
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  ABSTRACT: Cell death-inducing DNA fragmentation factor alpha-like effector A (CIDEA) regulates energy expenditure in the adipose tissue and is implicated in the development of obesity. A single nucleotide polymorphism in the CIDEA gene that causes an amino acid substitution of valine 115 to c(V115F) has recently been shown to be associated with obesity in the Swedish population. Here, we determined the effects of this polymorphism on phenotypes of metabolic syndrome within the Japanese population. Two hundred seventy unrelated Japanese male workers (mean age, 44.5 years) were analyzed in a cross-sectional study. The clinical features regarding metabolic syndrome, as well as CIDEA V115F polymorphism, were determined for each individual. The V115F polymorphism associated with waist circumference and fasting plasma glucose. These parameters were at higher levels in the VF + FF group than in the VV group (P < .05). The VF + FF group compared with the VV group had a higher prevalence for abdominal obesity (odds ratio [OR] = 1.89; 95% confidence interval [CI], 1.03-3.44), high fasting plasma glucose (OR = 2.81; 95% CI, 1.03-7.67), and metabolic syndrome (OR = 3.15; 95% CI, 1.05-9.48). These results suggest that the F allele of the CIDEA gene may serve as a risk factor for phenotypes related to metabolic syndrome in Japanese men.
  Metabolism 05/2008; 57(4):502-5. · 2.66 Impact Factor
• Article: Influence of CYP11B2 gene polymorphism on the prevalence of hypertension and the blood pressure in Japanese men: interaction with dietary salt intake.

  Yixuan Song, Koichi Miyaki, Jungo Araki, Ling Zhang, Yoshimitsu Takahashi, Takeo Nakayama, Masaaki Muramatsu
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  ABSTRACT: CYP11B2 gene encodes a key enzyme for the production of aldosterone. Our aim is to investigate the association of -344T/C polymorphism with hypertension in Japanese men. The interaction between genotypes and dietary salt intake was also considered. Three hundred and ten Japanese male workers participated in this study. Daily salt intake was calculated from a food frequency questionnaire. Melting curve analysis was used to determine CYP11B2 genotypes. There was a significant association between the CT + TT genotype and higher prevalence of hypertension (odds ratio: 3.03; p = 0.014). The association presented in a recessive manner and was strongest in the high-salt intake group (odds ratio: 9.44; p = 0.049). Only in the high-intake group, systolic blood pressure (SBP) was significantly higher in the CT + TT group than in the CC group (p = 0.038). The SBP had a positive correlation with salt intake in the CT + TT group (p for linear trend = 0.021), but not in the CC group (p for interaction = 0.011). CYP11B2 gene -344C/T polymorphism affects the risk of hypertension in Japanese men and high-salt intake levels strengthen this association. This gene-diet interaction warrants further study to elucidate the efficacy of salt restriction as an antihypertensive therapy in different genotypes.
  Journal of Nutrigenetics and Nutrigenomics 01/2008; 1(5):252-8. · 1.14 Impact Factor
• Article: The interaction between the interleukin 6 receptor gene genotype and dietary energy intake on abdominal obesity in Japanese men.

  Yixuan Song, Koichi Miyaki, Jungo Araki, Ling Zhang, Kazuyuki Omae, Masaaki Muramatsu
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  ABSTRACT: Previous reports have shown that the Asp358Ala (T/G) polymorphism of the interleukin 6 receptor (IL6R) gene is associated with obesity and type 2 diabetes mellitus, but few studies have examined this association in the Japanese population. We performed the current study to investigate the relationship between the IL6R Asp358Ala (T/G) polymorphism and obesity in healthy Japanese men. Two hundred eighty-five healthy Japanese men (age, 46.1 +/- 11.5 years [mean +/- SD]; waist circumference [WC], 83.9 +/- 9.3 cm; body mass index, 23.3 +/- 3.3 kg/m(2)) employed by a Japanese company were enrolled in this study. Height, weight, and WC were measured, and daily energy intake levels were assessed by self-reported questionnaires. Genotyping of polymorphisms was performed by using melting curve analysis; no association was found between IL6R genotype and WC or body mass index. However, when the subjects were stratified by IL6R genotype, an association between WC and dietary energy intake level was found in the TT + GT-type subjects (P for linear regression = .048), but not in GG subjects (P for linear regression = .555). In addition, logistic regression analysis revealed that the interaction of IL6R (GG vs TT + GT) genotypes and dietary energy intake levels affected risk for abdominal obesity (P for interaction = .030). We concluded that the IL6R Asp358Ala (T/G) polymorphism appears to interact with energy intake and affect abdominal obesity in Japanese men. The interaction of this genotype and energy intake warrants further study.
  Metabolism 08/2007; 56(7):925-30. · 2.66 Impact Factor
• Article: Polymorphisms in pro- and anti-inflammatory cytokine genes and susceptibility to atherosclerosis: a pathological study of 1503 consecutive autopsy cases.

  Kanae Oda, Noriko Tanaka, Tomio Arai, Jungo Araki, Yixuan Song, Ling Zhang, Aya Kuchiba, Takayuki Hosoi, Takuji Shirasawa, Masaaki Muramatsu, Motoji Sawabe
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  ABSTRACT: Atherosclerosis is a chronic inflammatory disease in the intima of the arterial wall, where cytokines play a crucial role in the pathogenesis of this disease. However, the question of whether or not genetic variations in the cytokine genes could influence the development of atherosclerosis has been poorly investigated. We investigated the relationship of nine common single-nucleotide polymorphisms (SNPs) in tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-10, IL-4 and transforming growth factor (TGF)-beta1 with the atherosclerotic severity in 10 different arteries based on 1503 consecutive autopsies of elderly Japanese subjects registered in the Japanese SNPs for geriatric research (JG-SNP) study. The -1031C allele of TNF-alpha was a significant protective factor for atherogenesis in the carotid, femoral and intracranial arteries [odds ratio (OR): 0.72, 0.73 and 0.70, respectively]. The -511T of IL-1beta and the +29T of TGF-beta1 were significant risk factors for atherogenesis in the subclavian and intracranial arteries (OR: 1.35 and 1.48, respectively). In contrast, conventional risk factors for atherogenesis, such as hypertension and diabetes mellitus, conferred independent risks for almost all arteries. Functional SNPs in TNF-alpha, IL-1beta and TGF-beta1 genes play a role in atherogenesis, although their influences are less pronounced than those of conventional risk factors and appear to be limited to specific arteries in the Japanese elderly.
  Human Molecular Genetics 04/2007; 16(6):592-9. · 7.64 Impact Factor
• Article: The relation between nicotinamide N-methyltransferase gene polymorphism and plasma homocysteine concentration in healthy Japanese men.

  Ling Zhang, Koichi Miyaki, Jungo Araki, Takeo Nakayama, Masaaki Muramatsu
  Thrombosis Research 02/2007; 121(1):55-8. · 2.44 Impact Factor
• Source

  Available from: Nakayama Takeo

  Article: Association between vitamin D receptor gene haplotypes and chronic periodontitis among Japanese men.

  Mariko Naito, Koichi Miyaki, Toru Naito, Ling Zhang, Keika Hoshi, Asako Hara, Katsunori Masaki, Shugo Tohyama, Masaaki Muramatsu, Nobuyuki Hamajima, Takeo Nakayama
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  ABSTRACT: The vitamin D receptor (VDR) is involved in a variety of biological processes, such as bone metabolism and modulation of the immune response. Recent findings suggest that the pathway involving bone mineral density-mediated effects is important for the development of periodontitis, but their effects of combined VDR gene polymorphisms have not been confirmed on periodontitis. We assessed the relationship between ApaI, BsmI, and FokI VDR polymorphisms and the risk of severe chronic periodontitis among Japanese adult men. In a cross-sectional study, we examined 97 unrelated healthy Japanese men (mean age: 45.6 years, range: 22-59). A clinical examination was performed at a worksite health checkup, and information was obtained using a self-reported questionnaire. DNA was extracted from whole blood, and the VDR ApaI, BsmI, and FokI polymorphisms were genotyped using polymerase chain reaction. F-carriers of FokI VDR polymorphisms were less likely to develop severe chronic periodontitis than non-F-carriers (p = 0.09). The ApaI and BsmI VDR polymorphisms did not show significant differences in the alleles or genotypes between the subjects with or without severe chronic periodontitis. The haplotype analysis of the three combined VDR polymorphisms revealed that the Abf homozygote had a notably higher prevalence of severe chronic periodontitis than the others, and adjustments for age, smoking status, number of teeth present, and prevalence of diabetes did not change this association (OR = 7.5; 95% CI = 1.6-34.4; p = 0.01). The VDR haplotype constructed from the ApaI, BsmI, and FokI polymorphisms is related to the risk of severe chronic periodontitis in Japanese men.
  International journal of medical sciences 02/2007; 4(4):216-22. · 2.24 Impact Factor
• Article: Interaction of angiotensin I-converting enzyme insertion-deletion polymorphism and daily salt intake influences hypertension in Japanese men.

  Ling Zhang, Koichi Miyaki, Jungo Araki, Yixuan Song, Tomomi Kimura, Kazuyuki Omae, Masaaki Muramatsu
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  ABSTRACT: The contribution of angiotensin I-converting enzyme insertion-deletion polymorphism (ACE I/D) to salt-sensitivity hypertension has been extensively studied by means of salt-loading tests, but whether or not the interaction with daily salt intake affects blood pressure still remains to be clarified. We therefore conducted a cross-sectional study of 284 Japanese male workers (age range, 20-64 years) to examine the effect of ACE I/D genotype and daily salt intake on hypertension. Blood pressure was measured and the ACE I/D was identified by polymerase chain reaction (PCR). Daily salt intake was calculated from a food frequency questionnaire (FFQ). In multivariate analyses, we explored the interaction of ACE I/D and salt intake by means of logistic regression analysis and multiple linear regression analysis. ACE I/D per se was not associated with blood pressure levels or hypertension. ACE I/D interacted with daily salt intake and correlated with hypertension (p for interaction = 0.047). In the ID+II genotype, hypertension was increased by high salt intake (p = 0.005), while in the DD genotype it was not (p = 0.257). The interaction was more prominent in the overweight group (p = 0.039) than in non-overweight group. In the overweight group, high salt intake induced a 10.5 mmHg higher diastolic blood pressure in the ID+II genotype than in the DD genotype (p = 0.042). Our results suggest that ACE I/D and daily salt intake constitute a gene-environment interaction, which may be further modulated by overweight.
  Hypertension Research 11/2006; 29(10):751-8. · 2.58 Impact Factor