Haplotype analysis on association between C-reactive protein gene and susceptibility to type 2 diabetes mellitus in Chinese Han population : CRP gene and type 2 diabetes mellitus.

AIMS: We aimed to evaluate the impact of C-reactive protein (CRP) gene polymorphism, additional gene-gene interaction, and haplotypes on susceptibility to type 2 diabetes mellitus (T2DM). METHODS: SNPstats online software ( https://www.snpstats.net/start.htm ) was employed to evaluate the association between CRP gene and T2DM risk. High-order interactions among SNPs was tested using generalized multifactor dimensionality reduction, and the testing balanced accuracy, training balanced accuracy and cross-validation consistency were calculated. The SHEsisPlus ( http://shesisplus.bio-x.cn/SHEsis.html ) online software was used for haplotype analysis. RESULTS: A total of 730 T2DM patients and 765 controls were enrolled. The T allele of rs1205 is associated with increased susceptibility to T2DM, OR (95% CI) were 1.51 (1.13-2.01), 1.44 (1.10-1.89) and 1.25 (1.01-1.54) for codominant, dominant and over-dominant models, respectively. We also found that minor allele of rs2794521 is associated with decreased susceptibility to T2DM under codominant and recessive models, OR (95%CI) were 0.38 (0.18-0.79) and 0.37 (0.16-0.80) for codominant and recessive models, respectively. No significant gene-gene interaction existed among CRP gene SNPs, all interaction p- values were more than 0.05. Haplotype analyses suggested the CGCA haplotype containing rs1205-C, rs1130864-G, rs2794521- C and rs3093059- A allele was associated with decreased risk of T2DM, OR (95% CI) = 0.83 (0.68-0.98), P = 0.047. CONCLUSIONS: Minor allele of rs1205 was associated with increased T2DM risk. Minor allele of rs2794521 and the CGCA haplotype were associated with decreased T2DM risk.

[Mild and moderate postpartum depression treated with acupuncture of Tiaoren Tongdu: a real world study].

OBJECTIVE: To observe the clinical therapeutic effect on mild and moderate postpartum depression treated with acupuncture of Tiaoren Tongdu (regulating the conception vessel and unblocking the governor vessel) on the base of real world. METHODS: A total of 116 patients with mild and moderate postpartum depression were divided into an acupuncture group (103 cases) and a non-acupuncture group (13 cases) according to treatment regimen provided. In the acupuncture group, acupuncture of Tiaoren Tongdu was applied to Baihui (GV 20), Yintang (GV 29), Zhongwan (CV 12), Qihai (CV 6), Guanyuan (CV 4), Neiguan (PC 6), Shenmen (HT 7), Hegu (LI 4), Zusanli (ST 36), Sanyinjiao (SP 6) and Taichong (LR 3). Needles were retained for 30 min each time, the treatment was given once every other day, 3 times a week. In the non-acupuncture group, psychotherapy was provided, once daily. The duration of treatment in the two groups was 8 weeks. According to the treatment times of acupuncture, the acupuncture group was subdivided into an acupuncture A group (60 cases with total treatments ≥ 6 times) and an acupuncture B group (43 cases with total treatments<6 times). Using propensity score matching method, the patients of the acupuncture A and B groups were matched each other. Finally, 31 pairs of cases were matched successfully. Before treatment, at 1st, 2nd, 4th and 8th weeks of treatment, as well as at 3-month follow-up, the scores of Hamilton depression scale (HAMD) were compared in patients among the three groups. Using Logistic regression, the impact of acupuncture frequencies on the therapeutic effect was analyzed and the clinical therapeutic effect was assessed. RESULTS: The total effective rate of the acupuncture A group was 100.0% (31/31), better than 76.9% (10/13) in the non-acupuncture group and 58.1% in the acupuncture B group (18/31) (P<0.05). HAMD score at each time point after treatment was lower than that before treatment in the patients of each group (P<0.05). But HAMD score at each time point after treatment in either the acupuncture A group or the acupuncture B group was lower than that in the non-acupuncture group separately (P<0.05), HAMD scores in the acupuncture A group at the 4th and 8th weeks of treatment and at follow-up were lower than those in the acupuncture B group (P<0.05). Logistic regression analysis showed that the total times of acupuncture treatment and the persistent days of treatment had a certain relation to therapeutic effect (P<0.05). CONCLUSION: Acupuncture of Tiaoren Tongdu effectively improves in mild and moderate postpartum depression and its therapeutic effect is closely related to treatment course.

Interaction of tobacco smoking and alcohol consumption with obesity on cardiovascular disease in a Chinese cohort.

OBJECTIVE: We aimed to detect the synergistic effect between alcohol drinking, smoking and obesity on incident cardiovascular disease (CVD) in a Chinese population- based cohort. METHODS: We performed this study based on a prospective cohort based on a Chinese population in Jiangsu, China. Logistic regression was employed to detect the interaction of smoking, drinking with obesity on susceptibility to CVD, and calculate the odds ratio (OR) of CVD and corresponding 95% confidence interval (CI). RESULTS: A total of 3598 subjects (1451 males and 2147 females) were enrolled, including 82 CVD patients (36 males and 46 females) who new developed CVD at the follow-up. We found a significant abdominal obesity-current smoking interaction on CVD risk. Compared to never-smokers with normal waist circumference, OR (95% CI) of CVD were 2.44 (1.56-3.81), 1.58 (0.93-2.69), and 5.37 (3.08-9.34) for smokers with normal waist circumference, abdominal obese nonsmokers and abdominal obese smokers, respectively. Synergy index for this interaction was 2.35 (1.05-4.50). We also found a significant abdominal obesity-alcohol drinking interaction on CVD. Compared to never-drinkers with normal waist circumference, OR (95% CI) of CVD were 1.57 (1.01-2.45), 1.84 (1.08-3.12), and 4.44 (2.55-7.72) for drinkers with normal waist circumference, abdominal obese non- drinkers and abdominal obese drinkers, respectively. Synergy index for this interaction was 2.44 (1.04-5.72). CONCLUSION: We found significant interactions between alcohol drinking and abdominal obesity, smoking and abdominal obesity on CVD risk, suggested that the effect of alcohol drinking or smoking on CVD susceptibility seems to be modified by abdominal obesity.

[Study on method for formulating clinical practice guidelines of common Chinese patent medicines based on clinical practices].

The clinical application of Chinese patent medicines has suffered sever problems and required guidelines for clinical practices. Currently, the expert consensus method is more suitable for formulating clinical practice guidelines of Chinese patent medicines than the evidence-based method. However, there remain problems in the application of the expert consensus method. This study proposed a derivative expert consensus method--a method for formulating clinical practice guidelines of common Chinese patent medicines based on clinical practices, and introduced the method in terms of research thought, methodology and implementation procedure.

Association of peroxisome proliferator-activated receptor γ polymorphisms and haplotypes with essential hypertension.

Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor involved in the regulation of several biochemical pathways. Blood pressure-lowering effects have been found in PPARγ agonists in several hypertensive models. The biology and research data related to the gene suggest that it could play a role in essential hypertension (EH) susceptibility. This study aimed to investigate the association between PPARγ polymorphisms and EH. About 820 subjects were genotyped for the three single-nucleotide polymorphisms used as genetic markers for the PPARγ genes (C681G, Prol2Ala, and C1431T). After correction for age, sex, smoking, alcohol consumption, body mass index, waist circumference, and fasting glucose, the G allele (CG+GG) of C681G was significantly associated with the increase in the risk of EH (odds ratio [OR]=1.54, 95%confidence interval [CI]: 1.14-2.09, p=0.005). The A allele (PA+PP) of Pro12Ala was significantly associated with the decrease in the risk of EH (OR=0.70, 95%CI: 0.52-0.95, p=0.020). However, C1431T was not significantly associated with EH. Generalized multifactor dimensionality reduction analysis showed that there was a potential gene-gene interaction between C681G and Prol2Ala (p=0.0107). The G-P haplotype (established by C681G, Prol2Ala) was significantly associated with increase in the risk of EH (OR=1.53, 95%CI:1.13-2.07, p=0.006). In conclusion, PPARγ polymorphisms and haplotypes were significantly associated with hypertension susceptibility.

Gene-gene interactions among PPARα/δ/γ polymorphisms for hypertriglyceridemia in Chinese Han population.

The peroxisome proliferator-activated receptors (PPARs)-α,-ß/δ and -γ are the ligand-activated transcription factors that function as the master regulators of glucose, fatty acid and lipoprotein metabolism, energy balance, cell proliferation and differentiation, inflammation and atherosclerosis. This study examined the main effects of both single-locus and multilocus interactions among genetic variants in Chinese Han individuals to test the hypothesis that PPAR-α/δ/γ polymorphisms may contribute to the etiology of hypertriglyceridemia independently and/or through such complex interactions. We genotyped 9 single nucleotide polymorphisms for PPAR-α/δ/γ. Participants were recruited from the Prevention of MetS and Multi-metabolic Disorders in Jiangsu Province of China Study. 820 subjects (474 non-hypertriglyceridemia subjects, 346 hypertriglyceridemia subjects) were randomly selected. Single-locus analyses showed that after adjusted for age, sex, smoking, alcohol consumption, body mass index, waist circumference and fasting glucose, rs1800206, rs9794, rs3856806 and rs1805192 were significantly associated with hypertriglyceridemia, the OR (95% CI) were 4.43(3.08-6.37), 1.49(1.10-2.02), 1.56(1.16-2.08), 2.43(1.80-3.29), respectively. Further, generalized multifactor dimensionality reduction method analysis showed that two-to-six-locus and eight-locus models were significant (p<0.05), which indicated a potential gene-gene interaction among PPAR-α/δ/γ polymorphisms. The results suggest that PPAR-α/δ/γ polymorphisms may contribute to the risk of hypertriglyceridemia independently and/or in an interactive manner.

[Genotype and haplotype analysis of peroxisome proliferators activated receptor α gene and the risk of essential hypertension].

OBJECTIVE: PPARα, which is expressed in the liver, heart, skeletal muscle, and kidney, regulates lipid and lipoprotein metabolism. The aim of this study was to investigate the association between the PPARα gene and essential hypertension (EH) using a haplotype-based cohort study in a Chinese-Han population. METHODS: 820 subjects (270 males, 550 females) were genotyped for the three single-nucleotide polymorphisms used as genetic marker for the PPARα gene (rs1800206, rs4253778 and rs135539). Individual polymorphism and haplotype data were available for analyses. RESULTS: In the dominant model, the presence of the G allele of rs1800206 and the C allele of rs135539 were at a decreased risk of EH (OR = 0.48, 95%CI 0.40 - 0.64, P < 0.01; OR = 0.75, 95%CI 0.62 - 0.93, P < 0.01, respectively). A 3.16-fold increase (95%CI 1.86 - 6.94, P = 0.002) in the risk of the development of EH was observed in homozygous genotype (CC) of rs4253778 compared to carriers of GG genotype (co-dominant model). The A-G-V and C-G-V haplotype (established by rs135539, rs4253778, rs1800206) was associated with a statistically significant decreased risk of EH (OR = 0.56, 95%CI 0.33 - 0.83, P = 0.027; OR = 0.53, 95%CI 0.30 - 0.84, P = 0.033, respectively). CONCLUSION: These results may help to clarify the role of PPARα gene in EH and the evaluation of its polymorphisms and haplotypes as being characterized as genetic decreased risk factors for EH.

[Effects of PPARD-87T > C and interactions with single nucleotide polymorphisms in PPARA and PPARG on abdominal obesity].

OBJECTIVE: To examine the main effect of 10 single nucleotide polymorphisms (SNPs) in contribution to abdominal obesity and study whether there is an interaction in the 10 SNPs in the cause of abdominal obesity. METHODS: A total of 820 subjects were randomly selected and no individual was related. Individual polymorphism and interactions were available for analyses. RESULTS: C allele carrier (CC + TC) was significantly higher than that of TT genotype (OR (95%CI) = 0.68 (0.52 - 0.90), P = 0.005). A 5-dimension gene-to-gene interaction model existed among rs135539, rs2016520, rs10865710, rs1805192 and rs709158 on the incidences of abdominal obesity. CONCLUSIONS: The C allele in rs2016520 is significantly associated with a lower rate of abdominal obesity. And there is an interaction among rs2016520, rs135539, rs10865710, rs1805192 and rs709158 on the incidences of abdominal obesity.

[Association of both peroxisome proliferator-activated receptor, gene-gene interactions and the body mass index].

OBJECTIVE: To investigate the association of ten single nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor (α, δ, γ) with obesity and the additional role of a gene-gene interaction among 10 SNPs. METHODS: Participants were recruited within the framework of the PMMJS (Prevention of Multiple Metabolic Disorders and Metabolic Syndrome in Jiangsu Province)-cohort-population-survey in the urban community of Jiangsu province, China. 820 subjects (513 non obese subjects, 307 obese subjects) were randomly selected and no individuals were related to each other. Ten SNPs (rs135539, rs4253778, rs1800206, rs2016520, rs9794, rs10865710, rs1805192, rs709158, rs3856806, rs4684847) were selected from the HapMap database, which covered PPARα, PPARδ and PPARγ. Logistic regression model was used to examine the association between ten SNPs in the PPARs and obesity. Odds ratios (OR) and 95% confident interval (95%CI) were calculated. Interactions were explored by using the Generalized Multifactor Dimensionality Reduction (GMDR). RESULTS: A group of 820 participants (mean age was 50.05± 9.41) was involved. The frequency of the mutant alleles of rs2016520 in obese populations was less than that in non-obese populations (26% vs. 33%, P < 0.01). The frequency of the mutant alleles of rs10865710 in obese populations was more than that in non-obese populations (37% vs. 31%, P = 0.01). C allele carriers had a significantly lower obesity occurrence than TT homozygotes [OR (95%CI) = 0.63 (0.47 - 0.84)] for rs2016520 but no significant association was observed between other SNP and incident obesity. GMDR analysis showed a significant gene-gene interaction among rs2016520, rs9794 and rs10865170 for the three-dimension models (P = 0.0010), in which prediction accuracy was 0.5834 and cross-validation consistency was 9/10. It also showed a significant gene-gene interactions between rs2016520 and rs10865170 in all the two-dimensional models (P = 0.0010), in which predictive accuracy was 0.5746 and cross-validation consistency was 9/10. CONCLUSION: Our data showed that rs2016520 was associated with lower obesity risk, as well as interactions among rs2016520, rs9794 and rs10865170 on incident obesity.

[Association between peroxisome proliferator-activated receptors gene polymorphism and essential hypertension].

OBJECTIVE: To investigate the association between ten single nucleotide polymorphism (SNP) in the peroxisome proliferator-activated receptor (PPAR) α/δ/γ and essential hypertension (EH). METHODS: Participants were recruited within the framework of a cohort populations survey from the PMMJS (Prevention of Multiple Metabolic Disorders and MS in Jiangsu Province) which was conducted in the urban community of Jiangsu province from 1999 to 2007. Eight hundred and twenty subjects (551 non-hypertensive subjects, 269 hypertensive subjects) were randomly selected but were not related to each other. Ten SNP (rs135539, rs1800206, rs4253778 of PPARα; rs2016520, rs9794 of PPARδ; rs10865710, rs1805192, rs4684847, rs709158 and rs3856806 of PPARγ) were selected from the HapMap database. χ(2) test was used to determine whether the whole population was in H-W genetic equilibrium. SHEsis software was used to examine the relations of SNP and linkage equilibrium. Logistic regression model was used to examine the association between ten SNP in the PPAR and EH. RESULTS: Difference on the distribution of four SNP genotypes including rs1800206, rs9794, rs10865710 and rs4684847 between high blood pressure and non-high blood pressure group, high systolic blood pressure (SBP) and normal SBP group, high diastolic blood pressure (DBP) and normal DBP group was significant (P < 0.05). After adjusting factors as age, sex, body mass index, fasting plasma glucose, high density lipoprotein cholesterol-C, high-fat diet and compared with wild-type gene carriers, the OR (95%CI) of objects with rs1800206 V allele appeared in high blood pressure, high SBP and high DBP were 0.60 (0.41 - 0.89), 0.57 (0.37 - 0.88) and 0.61 (0.39 - 0.96), respectively. The OR (95%CI) of objects with G allele of rs9794 were 0.63 (0.46 - 0.87), 0.51 (0.36 - 0.73) and 0.68 (0.47 - 1.01). The OR (95%CI) of objects with G allele of rs10865710 were 1.62 (1.19 - 2.20), 1.59 (1.14 - 2.22) and 1.53 (1.07 - 2.18), respectively. While the OR (95%CI) of objects with rs4684847 T allele were 1.42 (1.04 - 1.94), 1.38 (1.03 - 1.92) and 1.37 (1.00 - 1.88), respectively. CONCLUSION: The four SNPs including rs1800206 of PPARα, rs9794 of PPARδ and rs4684847, rs10865710 of PPARγ influenced high blood pressure, high SBP and high DBP to different degrees.

[Impact of lifestyle and obesity to the risk of type 2 diabetes: a prospective study in Jiangsu province].

OBJECTIVE: To investigate the relative contribution of lifestyle and obesity to the risk of developing type 2 diabetes. METHODS: All baseline survey data were based on the program Prevention of Multiple Metabolic Disorders and Metabolic Syndrome in Jiangsu Province (PMMJS) which was conducted during April 1999 to May 2004. In the baseline survey, 8685 participants were selected using multi-stage sampling method. Frem March 2006 to November 2007, 4582 participants who had been in the study for at least 5 years were included in the follow-up survey. A total of 3847 participants were followed and of them 3461 non-diabetic subjects were included in this analysis. High fat diet or not, low fiber diet or not, sedentary or not and occupational physical activity classification were defined as lifestyle variables and the incidence of type 2 diabetes at follow-up survey was defined as outcome variable. It was prospectively examined that the separate and joint association of lifestyle and obesity with the development of type 2 diabetes in subjects recruited from PMMJS, using logistic regression model. RESULTS: A total of 162 incident cases of type 2 diabetes during 6.3 years of follow-up in total 3461 participants were documented. The incidence rate was 4.7%. After adjusted for sex, age, family history of diabetes, blood pressure, lipids and fast plasma glucose, risk of type 2 diabetes increased with lighter occupational physical activity (compared with vigorous group, moderate group aRR = 2.15, 95%CI: 1.26 - 3.68; light group aRR = 2.39, 95%CI: 1.12 - 4.87), sedentary lifestyle (aRR = 2.94, 95%CI: 1.90 - 4.54), low fiber diet (aRR = 1.58, 95%CI: 1.01 - 2.53), overweight (aRR = 1.33, 95%CI: 1.01 - 1.90) and obesity (aRR = 1.59, 95%CI: 1.07 - 3.75). In joint analysis of lifestyle and obesity, the impact of sedentary lifestyle (in BMI < 25 group, aRR = 3.42, 95%CI: 1.99 - 5.86; in BMI ≥ 25 group, aRR = 2.41, 95%CI: 1.13 - 5.12) and low fiber diet (in BMI < 25 group, aRR = 1.42, 95%CI: 0.81 - 2.54; in BMI ≥ 25 group, aRR = 2.63, 95%CI: 1.15 - 6.03) on diabetes were independent of overweight and obesity. When stratified by sedentary lifestyle or low fiber diet, there was no association between overweight/obesity and diabetes risk (sedentary aRR = 2.04, 95%CI 0.87 - 4.71, non sedentary aRR = 1.21, 95%CI: 0.82 - 1.78; non low fiber diet aRR = 1.26, 95%CI: 0.87 - 1.84, low fiber diet aRR = 1.88, 95%CI: 0.80 - 4.80). CONCLUSION: Unhealthy lifestyle, overweight and obesity independently increase the risk of type 2 diabetes. The magnitude of risk contributed by sedentary lifestyle and low fiber diet are much greater than that imparted by overweight and obesity.

[A prospective study on the association between dynamic change of waist circumference and incident hypertension].

OBJECTIVE: To study the impact on dynamic change of waist circumference (WC) through follow-up data on the incidence of hypertension in several cohort groups. METHODS: In this prospective study, 2778 free-hypertension subjects were recruited from a program "Prevention of Multiple Metabolic disorders and metabolic syndrome (MS) in Jiangsu province" (PMMJS) to evaluate the risk of hypertension in relation to WC dynamic change on normal WC or abnormal obesity group. Dynamic change of WC was measured by WC D-value, which was expressed by data on the difference of WC between baseline and the first follow up. Study outcome was defined as incident hypertension during the first to the second follow up period in this study. The association between dynamic change of WC and incident hypertension was analyzed by using Cox proportional hazards regression model. RESULTS: There were 2778 participants, 660 subjects developed hypertension during the follow-up, regardless of the normality of the baseline WC, the risk of hypertension increased across the tertiles of WC, while the incidence of hypertension was higher in non-control group than that in control group. In populations with abdominal obesity and normal WC at baseline, RRs (95%CI) of hypertension were 1.95 (1.19 - 3.19) and 2.38 (1.89 - 2.99) in subjects with abdominal obesity seen at the first follow up period, compared to subjects with normal WC in the same period. After adjustment for gender, age and other hypertension related risk factors, in populations with abdominal obesity and normal WC at baseline survey, RRs (95%CI) of hypertension were 4.36 (1.69 - 9.74) and 1.44 (1.03 - 2.35) respectively, for the non-control group. CONCLUSION: WC dynamic change was associated with hypertension, WC control while WC reduction was important for early prevention on hypertension.

Study strategies for acupuncture treatment of chronic nonbacterial prostatitis.

By retrospectively reviewing the current status of traditional Chinese medicine (TCM) and Western medicine treatments of chronic nonbacterial prostatitis (CNP), the TCM understanding of its etiologies and pathogenesis, the therapeutic principles and the mechanisms of acupuncture treatment of CNP, the clinical study strategies of acupuncture treatment for CNP were further proposed, which could provide more scientific basis and support for the definite longer-term therapeutic efficacy of acupuncture treatment of CNP. Breakthrough in the treatment of CNP will be achieved with the application of acupuncture therapy both in clinical practice and experimental research.

Research advances in treatment of cerebral ischemic injury by acupuncture of conception and governor vessels to promote nerve regeneration.

Cerebral ischemia is one of the most common diseases treated by acupuncture therapeutics. Recent studies indicated that acupuncture treatment by needling the conception and governor vessels had positive effects in promoting neural regeneration in patients after cerebral ischemia injury. Acupuncture intervention could continuously promote the proliferation and differentiation of the neural stem cells in the brain, obviously up-regulate expression of growth factors, accelerate angiogenesis and inhibit apoptosis. Hence, it is necessary to present an exhaustive review on the mechanisms. The present review gives a detailed description of pathological changes of cerebral ischemia and acupuncture intervention applied to the conception and governor vessels, and proposes research prospects in the future.

[Gene-gene interactions among the peroxisome proliferator-activated receptor polymorphisms for hypertriglyceridemia].

OBJECTIVE: To investigate the association of ten SNP at peroxisome proliferator-activated receptors (PPARα, δ, γ) with hypertriglyceridemia and the gene-gene interaction. METHODS: Participants were recruited from the Prevention of MetS and Multi-metabolic Disorders in Jiangsu province of China Study (PMMJS). A total of 820 subjects were selected from the 4083 participants who had received follow-up examination, by using simple random sampling. Participants in baseline and follow-up study surveys were both collected blood samples 11 ml in the morning after at least 8 hours of fasting. Blood samples which collected at the baseline were subjected to PPARα, PPARδ and PPARγ genotype analyses. Blood samples which collected at the follow-up were used to measure serum triglyceride levels. The logistic regression model was used to analyze the association between different SNP and hypertriglyceridemia, and the generalized multifactor dimensionality reduction (GMDR) was applied to explore the gene-gene interaction. RESULTS: The samples included 474 in the non-hypertriglyceridemia group and 346 in the hypertriglyceridemia group. The genotype frequencies of rs1800206 in the hypertriglyceridemia group were 211 (61.0%) for LL, 132 (38.2%) for LV and 3 (0.9%) for VV, and in the non-hypertriglyceridemia group were 411 (86.7%) for LL, 59 (12.4%) for LV and 4(0.8%) for VV (χ(2) = 74.18, P < 0.01). V allele frequencies of rs1800206 in the hypertriglyceridemia group was 138(19.9%), and in the non-hypertriglyceridemia group was 67 (7.1%) (χ(2) = 60.62, P < 0.01). The genotype frequencies of rs2016520 in the hypertriglyceridemia group were 177 (51.2%) for TT, 154 (44.5%) for TC and 15 (4.3%) for CC, and in the non-hypertriglyceridemia group were 211 (44.5%) for TT, 212 (44.7%) for TC and 51 (10.8%) for CC(χ(2) = 15.93, P < 0.01). C allele frequencies of rs2016520 in the hypertriglyceridemia group was 184(26.6%), and in the non-hypertriglyceridemia group was 314 (33.1%) (χ(2) = 8.07, P < 0.01). The genotype frequencies of rs3856806 in the hypertriglyceridemia group were 149 (43.1%) for CC, 156 (45.1%) for CT and 41 (11.8%) for TT, and in the non-hypertriglyceridemia group were 269 (56.8%) for CC, 170 (35.9%) for CT and 35 (7.4%) for TT (χ(2) = 15.93, P < 0.01). T allele frequencies of rs3856806 in the hypertriglyceridemia group was 238(34.4%), and was 240 (25.3%) in the non-hypertriglyceridemia group (χ(2) = 15.96, P < 0.01). The genotype frequencies of rs1805192 in the hypertriglyceridemia group were 145 (41.9%) for PP, 158(45.7%) for PA and 43(12.4%) for AA, and in the non-hypertriglyceridemia group were 314 (66.2%) for PP, 137(28.9%) for PA and 23(4.9%) for AA (χ(2) = 50.92, P < 0.01). A allele frequencies of rs1805192 in the hypertriglyceridemia group was 244(35.2%), and was 183 (19.3%) in the non-hypertriglyceridemia group(χ(2) = 52.89, P < 0.01). After adjusting age, gender, smoking, alcohol consumption, high-fat diet, low -fiber diet and occupational physical activity factors, rs1800206, rs2016520, rs3856806 and rs1805192 were significantly associated with hypertriglyceride, while the OR (95%CI) was 3.88 (2.69 - 5.60), 0.71 (0.52 - 0.96), 1.40 (1.03 - 1.90) and 2.56 (1.88 - 3.49), respectively (P < 0.05). GMDR model analysis showed that the second-order model (rs1800206 and rs1805192) was the best model when quality traits of triglyceride was chosen as outcome (P < 0.01); while third-order model (rs1800206, rs1805192 and rs2016520) was the best model when quantitative traits of triglyceride was chosen as outcome (P < 0.01). CONCLUSION: The rs1800206, rs2016520, rs3856806 and rs1805192 were significantly associated with hypertriglyceridemia. There was a gene-gene interaction between multiple SNP.

Gene-gene interaction between PPARδ and PPARγ is associated with abdominal obesity in a Chinese population.

The peroxisome proliferator-activated receptors (PPARs) -α, -δ/ß and -γ are the ligand-activated transcription factors that function as the master regulators of glucose, fatty acid and lipoprotein metabolism, energy balance, cell proliferation and differentiation, inflammation, and atherosclerosis. The objective of the current study was to examine the main and interactive effect of seven single nucleotide polymorphisms (SNPs) of PPARδ/γ in contribution to abdominal obesity. A total of 820 subjects were randomly selected and no individuals were related. The selected SNPs in PPARδ (rs2016520 and rs9794) and PPARγ (rs10865710, rs1805192, rs709158, rs3856806, and rs4684847) were genotyped. Mean difference and 95% confident interval were calculated. Interactions were explored by the method of generalized multifactor dimensionality reduction. After adjustment for gender, age, and smoking status, it was found that the carriers of the C allele (TC + CC) of rs2016520 were associated with a decreased risk of abdominal obesity compared to the carriers of the TT genotype (mean difference = -2.63, 95% CI = -3.61--1.64, P < 0.0001). A significant two-locus model (P = 0.0107) involving rs2016520 and rs10865710 and a significant three-locus model (P = 0.0107) involving rs2016520, rs9794, and rs1805192 were observed. Overall, the three-locus model had the highest level of testing accuracy (59.85%) and showed a better cross-validation consistency (9/10) than two-locus model. Therefore, for abdominal obesity defined by waist circumference, we chose the three-locus model as the best interaction model. In conclusion, the C allele in rs2016520 was significantly associated with a lower abdominal obesity. Moreover, an interaction among rs2016520, rs1805192, and rs9794 on incident abdominal obesity could be demonstrated.

[Interaction of both hypertriglyceridemic waist and impaired fasting glucose on the incidence of diabetes mellitus].

OBJECTIVE: To study the use of hypertriglyceridemic waist (HTGW) to predict the occurrence of diabetes. Also to independently study whether there was an interaction between HTGW and impaired fasting glucose impaired fasting glucose (IFG) on the cause of diabetes. METHODS: We undertook a cohort study based on data from the "Prevention of Multiple Metabolic Disorders and Metabolic Syndrome (MS) Study in Jiangsu Province, China". We used the logistic regression model to analyze the relations between both HTGW, IFG and diabetes mellitus and to evaluate the multiplied interaction between HTGW and IFG to include product terms method. Counting additive interaction was carried out under the Excel Calculation Sheet, compiled by Anderson and his colleagues. RESULTS: After adjusted for general risk factors and baseline fasting plasma glucose (FPG), results showed that subjects with HTGW had a 2.10 (95% CI: 1.36 - 3.25) adjusted relative risk (HR) of developing a diabetes when compared with those individuals without HTGW at the baseline study. When IFG was stratified, participants with HTGW were significantly associated with diabetes, regardless of IFG. The multi-adjusted HRs of diabetes were 3.09 (1.70 - 5.61) and 2.09 (1.08 - 4.02), respectively. Compared to the participants with non-HTGW and their FPG level below the threshold, those having HTGW and their FPG level was above the threshold, had the highest adjusted HR values [12.05 (95% CI: 6.89 - 21.07)]. Data from the additive interaction analysis showed that RERI as 7.00 (95% CI: 0.49 - 13.51), AP as 0.57 (95% CI: 0.32 - 0.82) and SI as 2.66 (95% CI: 1.36 - 5.21). CONCLUSION: HTGW could predict the occurrence of diabetes, independent from IFG while the presence of HTGW with IFG could have an additive interaction on the cause of diabetes.

[Association and interaction of peroxisome proliferator-activated receptor α with low high-density lipoprotein hyperlipidemia and with peroxisome proliferator-activated receptor γ].

OBJECTIVE: To investigate the association of ten single nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptors (α, δ, γ) with low high-density lipoprotein-cholesterol (HDL-C) hyperlipidemia and the additional role of a gene-gene interactions among the 10 SNPs. METHODS: Participants were recruited under the framework of the PMMJS (Prevention of Multiple Metabolic Disorders and MS in Jiangsu Province) cohort populations survey, in the urban community of Jiangsu province, China. 820 subjects (579 normal HDL-C, 241 low HDL-C) were randomly selected, with one of them related to each other. Ten SNPs (rs135539, rs4253778, rs1800206, rs2016520, rs9794, rs10865710, rs1805192, rs709158, rs3856806, rs4684847) were selected from the HapMap database, which covered PPARα, PPARδ and PPARγ. Logistic regression model was used to examine the association between ten SNPs in the PPARs and low HDL-C. Odds ratios (OR) and 95% confident interval (95%CI) were calculated. Interactions were explored by using the method of Generalized Multifactor Dimensionality Reduction (GMDR). RESULTS: After adjusting the factors as age, sex, smoking status, occupational physical activity, high-fat diet as well as low-fiber diet, both rs135539 and rs1800206 were significantly associated with the incidence of low HDL-C, with the OR (95% CI) values as 1.46 (1.07 - 1.99) and 0.62 (0.42 - 0.90). No statistically significant difference was found between other SNPs and the occurrence of low HDL-C. Data from GMDR analysis showed significant gene-gene interaction among rs135539, rs4253778 of PPARα and rs10865710, rs3856806, rs709158 and rs4684847 of PPAR γ (P = 0.0107). CONCLUSION: PPARα rs135539 was associated with the occurrence of low HDL-C, and had interacted with rs4253778, rs10865710, rs3856806, rs709158 and rs4684847.

[Impact of dynamic change of waist circumference or body mass index in hypertension incidence].

OBJECTIVE: To study the impact of dynamic change of waist circumference (WC) and body mass index(BMI) in two years on hypertension incidence in cohort populations. METHODS: A perspective cohort study was conducted. The participants (5888 subjects) whose follow-time were 2 years or longer from the program Prevention of multiple metabolic disorders and metabolic syndrome (MS) in Jiangsu province were investigated. Amongst 5888 subjects, 4582 participants received the first follow-up investigation in January 2002. Among 4582 subjects who received first follow-up investigation and whose follow-time met 5 years, total 3847 participants received the second follow-up investigation in March 2006. Total 2778 free hypertension subjects were included in this analysis. Subjects with normal WC or BMI at baseline but abnormal WC or BMI at the first follow-up or subjects with abnormal WC or BMI both at baseline and the first follow-up were defined as non-control group. Subjects with abnormal WC or BMI at baseline but normal WC or BMI at the first follow-up or subjects with normal WC or BMI both at baseline and the first follow-up were defined as control group. The incidence of hypertension at second follow-up investigation was defined as the final variable(hypertension = 1, non-hypertension = 0). The association between dynamic change of WC or BMI and incident hypertension was analyzed by using Cox proportional hazards regression model. The OR, RR value and 95%CI were calculated through WC and BMI risk stratification. RESULTS: Among 2778 participants without hypertension at baseline, 660 subjects developed hypertension. When both BMI difference value (D-value) and WC D-value were included in the regression model, WC D-value was associated with hypertension in both genders (males: OR = 1.04, 95%CI: 1.01 - 1.05; females: OR = 1.04, 95%CI: 1.02 - 1.06), but BMI D-value was not associated with hypertension in both men and women (males: OR = 1.04, 95%CI: 0.97 - 1.11; females: OR = 0.98, 95%CI: 0.93 - 1.03). Hypertension risk of WC non-control group was higher than that in WC control group in baseline normal and abnormal WC groups (normal baseline WC group: RR = 1.41, 95%CI: 1.01 - 2.39, abnormal baseline WC group: RR = 4.41, 95%CI: 1.66 - 9.80). But in baseline abnormal BMI group, there was no significant difference between BMI control and non-control group (RR = 1.33, 95%CI: 0.88 - 2.02). Whether BMI was controlled can not influence hypertension risk if WC was controlled (males: RR = 1.03, 95%CI: 0.36 - 2.96; females: RR = 1.02, 95%CI: 0.70 - 5.85), however, control WC could reduce hypertension risk obviously even though BMI was not controlled (males: RR = 4.03, 95%CI: 1.61 - 10.09; females: RR = 1.55, 95%CI: 1.13 - 3.60). CONCLUSION: Both WC and BMI dynamic change were associated with change of hypertension. But reducing WC can decrease hypertension risk more than reducing BMI.