PPAR α and PPAR γ polymorphisms as risk factors for dyslipidemia in a Chinese Han population.

BACKGROUND: The PPAR α and PPAR γ are the key messengers responsible for the translation of nutritional stimuli into changes for the expression of genes, particularly genes involved in lipid metabolism. However, the associations between PPAR α/γ polymorphisms and lipid serum levels in the general population were rarely studied, and the conclusions were conflicting. The objective was to investigate the associations of the PPAR α and PPAR γ polymorphisms with dyslipidemia. METHODS: 820 subjects were randomly selected from the Prevention of Multiple Metabolic Disorders and MS in Jiangsu Province cohort populations. The logistic regression model was used to examine the association between these polymorphisms and dyslipidemia. SNPstats was used to explore the haplotype association analyses. RESULTS: In the codominant and log-additive models, rs1800206, rs1805192 and rs3856806 were all associated with dyslipidemia (P < 0.005). When the most common haplotype L-G (established by rs1800206, rs4253778) was treated as the reference group, the V-G haplotype was associated with dyslipidemia (P < 0.001), higher TC and TG levels (P < 0.01). Moreover, when compared to Pro-C haplotype (established by rs1805192, rs3856806), the Pro-T, Ala-C, Ala-T haplotypes were associated with dyslipidemia (p < 0.001). A-T haplotype was associated with higher TC levels, (p < 0.01), and the P-T, A-C, A-T haplotypes were associated with higher TG levels (p < 0.01). CONCLUSIONS: PPAR α and PPAR γ polymorphisms and haplotypes may be the genetic risk factors for dyslipidemia.

[The prospective study of association between C-reactive protein and hypertension in community population].

OBJECTIVE: The aim was to explore the association between high-sensitivity C-reactive protein level at baseline and hypertension in follow-up periods in a Chinese cohort. METHODS: We analyzed data from a cohort established in "Prevention of metabolic syndrome and multi-metabolic disorders in Jiangsu province" in April 2000. A follow-up investigation was carried out for those whose follow up time met 5 years in June 2006. A total of 2035 persons completed investigation and hs-CRP was tested. Subjects with normal baseline blood pressure were classified into four groups(514, 498, 515 and 508 subjects in each group) according to quartiles of hs-CRP level (<1.3, 1.3-1.9, 2.0-3.2 and ≥ 3.3 mg/L). The relationship between the risk of hypertension and baseline level of hs-CRP were analyzed using Cox proportional hazards regression model. RESULTS: The median of follow up time was 6.39 years among the 2035 subjects (926 males and 1109 females). Hypertension incidence was 2378/100 000 person-years, 2942/100 000 person-years, 3693/100 000 person-years and 4390/100 000 person-years in hs-CRP < 1.3, 1.3-1.9, 2.0-3.2 and ≥ 3.3 mg/L groups respectively. Compared to the group of hs-CRP < 1.3 mg/L, the relative risk (RR) (95%CI) of hypertension in groups of hs-CRP 1.3-1.9, 2.0-3.2 and ≥ 3.3 mg/L was 1.22 (0.87-1.72), 1.43 (1.03-2.00), 1.70 (1.21-2.41) respectively, adjusted for sex, age, baseline blood pressure, BMI, smoking, alcohol drinking, physical activity and family history of myocardial infarction and diabetes.When stratified by quartiles of baseline blood pressure, the incidence of hypertension in each group increased with level of hs-CRP.In the group whose baseline SBP < 110 mm Hg (1 mm Hg = 0.133 kPa) , compared to the group of hs-CRP < 1.3 mg/L, RR (95%CI) were 2.24 (1.32-4.03), 2.57 (1.57-4.57) and 3.57 (2.54-5.90) in hs-CRP 1.3-1.9, 2.0-3.2 and ≥ 3.3 mg/L groups respectively.In the group whose baseline DBP < 65 mm Hg, RR (95%CI) were 1.78 (1.03-3.24), 2.74 (1.63-4.93) and 4.13 (2.35-7.27) respectively. CONCLUSION: Inflammation was an important process in the development of hypertension.

[Current status and urban-rural comparison of clinical agency of detection, management, and health insurance for hypertensive patients in communities of five provinces in China in 2010].

OBJECTIVE: To investigate the status of the clinical agency of detection, management, and health insurance for hypertensive patients in urban and rural communities of five provinces in China in 2010, in order to provide fundamental data for implementation and evaluation of community health management of hypertensive patients in basic public health service. METHODS: From Jiangsu, Shandong, Hebei, Sichuan and Gansu provinces, cities and districts (counties) were selected according to economic development level and 10 survey sites were finally determined. In each survey site, 3-4 communities or townships were selected by cluster sampling methods in 2010. A total of 8326 eligible hypertensive patients (4363 in urban and 3963 in rural) were included. The urban-rural difference of clinical agency and health insurance was compared for hypertensive patients. RESULTS: In urban areas, 43.74% (1867/4268) hypertensive patients were first diagnosed at hospitals of district level or above, 25.07% (1070/4268) at community health service centers (CHSC), and 20.20% (862/4268) at community health service stations (CHSS), respectively; 30.72% (1274/4147) and 31.11% (1290/4147) patients chose CHSC and CHSS for their follow-up visiting, respectively; 60.23% (3073/5102) antihypertensive medication was obtained from pharmacies. In rural areas, 54.58% (2133/3908) hypertensive patients were first diagnosed at village clinics, 22.36% (874/3908) at township hospitals, and 18.86% (737/3908) at hospitals of county level or above; 70.49% (2695/3823) patients chose village clinics for their follow-up visiting; 46.23% (2116/4577) antihypertensive medication was obtained from village clinics, and 36.29% (1661/4577) from pharmacies. The main reasons for choosing clinical agency for both urban and rural patients were convenience (45.79%, 6276/13 706) and low cost (11.78%, 1614/13 706). The proportions of reimbursements for hospitalization expenses and total medical expenses for hypertensive patients in urban in the past year were 66.67% and 34.78%, respectively, which were much higher than those in rural (35.71% and 9.50%) (Z value was -12.13 and -17.56, P < 0.01). CONCLUSION: Community-based hypertension detection and routine blood pressure measurement during clinical visiting should be further strengthened to improve early diagnosis of hypertension. The development of community-based clinical agency should be able to provide convenient and low cost health service for hypertensive patients to improve treatment, follow-up and control of hypertension.

[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.

[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.

[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.

[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.

[The analysis of drug cost and direct medical expense in community health management of hypertensive patients].

OBJECTIVE: To investigate the current situation of drug cost, hospitalization cost and direct medical expense in community health management of hypertensive patients, in order to lay foundation for evaluating whether the community health management in basic public health service has cost-effect in Health Economics. METHODS: A total of 8326 hypertensive patients from 10 survey pilots in 5 provinces were selected by cluster sampling methods, including 3967 patients who took part in community health management for over 1 year as management group and 4359 cases who have never taken part in community health management as control group. The essential information of research objects were collected by questionnaire; and the medical cost information in the last year (from November 2009 to November 2010) were collected retrospectively. The different annual medical treatment cost, hospitalization cost and direct medical expense in the two groups were compared and analyzed. RESULTS: The average annual drug cost in hypertension was (621.50 ± 1337.78) yuan per patient; while the cost was (616.13 ± 1248.40) yuan in management group and (626.44 ± 1414.30) yuan in control group respectively. The average annual drug cost of hypertensive patients who took medicine therapy was (702.05 ± 1401.79) yuan per person, while the cost in the management group ((688.50 ± 1300.70) yuan) was much lower than it in control group ((714.64 ± 1489.60) yuan). The annual average drug cost in urban was (731.88 ± 1403.31) yuan per person, which was higher than it in rural as (407.44 ± 1171.44) yuan per person. The average hospitalized rate was 12.2% (1014/8326), and the average annual cost among the hospitalized patients was (9264.47 ± 18 088.49) yuan per person; while the cost was (7583.70 ± 13 267.00) yuan in management group, which was lower than it in control group as (11 028.00 ± 21 919.00) yuan. The average annual hospitalized cost in hypertension was (1064.87 ± 6804.83) yuan per person; while the cost was (936.73 ± 5284.90) yuan in management group, which was lower than it in control group as (1181.50 ± 7937.90) yuan. The average annual direct medical expense in hypertension was (2275.08 ± 8225.66) yuan per person; while the expense was (2165.10 ± 6564.60) yuan in management group and (2375.20 ± 9487.60) yuan in control group. The average annual direct medical expense in urban ((2801.06 ± 9428.54) yuan per person) was higher than it in rural ((1254.70 ± 4990.27) yuan per person). CONCLUSION: The community health or standardized management of hypertensive patients can reduce the average annual drug cost and hospitalization cost (around 26 yuan and 245 yuan separately); and thereby save the annual direct medical expense per capita in hypertension (around 210 yuan). In the reform and development of national medical health system, we should enhance and promote the standardized community health management of hypertensive patients.

Construction of a novel Zn-Ni trinuclear Schiff base and a Ni2+ chemosensor.

A novel Zn-Ni heterotrinuclear Schiff base compound bearing acacen(2-) moieties was constructed through the selective assembly of a chemosensor Schiff base zinc compound with a Ni(2+) ion. Its crystal structure not only clearly explains the binding mode between the chemosensor molecule and the detected metal ion but also represents the first trinuclear complex based on a symmetric acacen(2-) base Schiff base.

Single-crystal-to-single-crystal transformation in a one-dimensional Ag-Eu helical system.

Single-crystal-to-single-crystal transformation of one-dimensional 4d-4f coordination polymers has been investigated for the first time. More importantly, we observed the transformation of a meso-helical chain to a rac-helical chain as a function of the temperature.

[A comparison of applicability in three diagnostic criteria of metabolic syndrome in Jiangsu population].

OBJECTIVE: To compare the applicability of the three diagnostic criteria for metabolic syndrome (MS) proposed by the International Diabetes Federation (IDF) in 2005, Adult Treatment Panel III of National Cholesterol Education Program (NCEP-ATP III) in 2005 and Chinese Diabetes Socie (CDS) in 2004. METHODS: Based on the findings of cohort study of multiple metabolic disorders and metabolic syndrome (1971 cases) in Jiangsu province, MS was diagnosed according to these three definitions respectively, and by calculating the sensitivity, specificity, and ROC curve distance, those with lower false positive and false negative rates were identified as to detecting cardio vascular diseases (CVD) and type 2 diabetes mellitus (T2DM). While, through Cox regression analysis, to compare their relative risk (RR) and 95% confidential interval (CI) was wade. RESULTS: Among three diagnostic criteria, the specificity by CDS of MS was higher than the other criteria (83.52%, 76.36%, 89.57%; 85.02%, 78.67%, 92.28%), however the sensitivity of CDS of MS was low (40.82%, 29.47%). When using CDS, over 50 percent of diagnosis might be missed. ATP III definition corresponded to the shortest distance in ROC curve, namely, at the diagnostic criteria, the rates of false positive and false negative for identifying clustering of CVD and T2DM were minimum (0.4369; 0.5777). The incidence of CVD [5.59 (2.62 - 11.92) vs 2.90 (1.41 - 5.93)], T2DM [3.36 (1.92 - 5.79) vs 1.97 (1.16 - 3.34)] was significantly higher in cases of ATP III+/IDF-than ATP III+/IDF+, as compared with ATP III-/IDF-. CONCLUSION: Among three diagnostic criteria, the ATP III definition of the MS should be the most applicable diagnostic criteria for MS in Jiangsu population.

Bis[methyl 2-(2-pyridylmethyl-idene)hydrazinecarbodithio-ato]zinc(II).

In the title compound, [Zn(C(8)H(8)N(3)S(2))(2)], the Zn atom is coordinated by the two ligands in a tridentate manner, via the pyridyl N, the azomethine N and the thiol-ate S atom; the coordination geometry is distorted octa-hedral, with the two ligands in the mer configuration (two S atoms and two pyridyl N atoms are cis with respect to each other and the azomethine N atoms is trans). The mol-ecules are linked by C-H⋯S hydrogen bonds, forming a three-dimensional network structure.

Haplotype Analysis of PPARγ Gene Polymorphisms and the Lipoprotein (a) Level.

BACKGROUND: Lipoprotein (a) [Lp(a)], as an independent risk factor for cardiovascular disease, is more likely to be genetically determined according to the increasing evidence of epidemiologic and clinical studies in recent years. Peroxisome proliferator-activated receptor (PPAR) γ, the ligand-activated transcription factors, was considered as an indispensable role in the process of lipid metabolism. This study was designed to explore the associations of three single-nucleotide polymorphisms (SNPs) and the haplotypes of the peroxisome proliferator-activated receptor (PPAR)γ gene with the level of Lp(a). METHODS: Participants were recruited under the framework of the PMMJS (The Prevention of Metabolic Syndrome (MS) and Multi-metabolic Disorders in Jiangsu Province of China Study) from Apr 1999 to Jun 2004. Overall, 644 subjects were randomly selected and 3 SNPs of PPARγ gene (rs10865710, rs1805192, rs4684847) were genotyped. RESULTS: After adjusting for age, sex, cigarette smoking, alcohol drinking, waist circumference and body mass index, rs4684847 was significantly associated with Lp (a). The presence of the rs4684847 T allele (CT+TT) have a lower level of Lp (a) than the allele (CC) in the dominant model, mean difference was -27.30 (95% CI: -52.88∼-1.73) mg/L, P<0.05. G-P-T and G-A-T haplotype were associated with lower levels of Lp (a) (P=0.0041 and <0.0001), mean difference was 49.79 (95% CI: -97.52∼-2.06) mg/L and 17.75 (95% CI: -25.75∼-9.75) mg/L. CONCLUSION: PPAR gamma polymorphisms (rs10865710, rs1805192, rs4684847) and haplotypes may be the genetic risk factors for Lp (a) level.

Association and interaction of PPARα, δ, and γ gene polymorphisms with low-density lipoprotein-cholesterol in a Chinese Han population.

AIMS: Elevated low-density lipoprotein-cholesterol (LDL-C) is regarded as one of major risks of cardiovascular diseases and atherosclerotic events. It has been previously reported that peroxisome proliferator-activated receptors (PPARs) play an important role in the regulation of lipid metabolism. In this study, we aimed to investigate the influence of PPARα/δ/γ gene polymorphisms on LDL-C level. Eight hundred twenty unrelated participants were recruited. Ten single-nucleotide polymorphisms (SNPs) were genotyped to analyze the gene-gene interactions among these polymorphisms using the generalized multifactor dimensionality reduction (GMDR) method. RESULTS: The results of single-locus analyses indicated that the genotypes with minor allele variants at the rs1800206, rs9794, rs1805192, rs709158, and rs3856806 loci are associated with higher LDL-C levels (p<0.05) after adjusting for covariates. In contrast, individuals that were homozygous for the major allele (CC) of rs10865710 had significantly higher LDL-C than those with either one or more minor type alleles (CG+GG, mean difference: -0.21 mM; 95% confidence interval [CI]: -0.37 to -0.04 mM; p=0.013). Significant gene-gene interactions among PPAR gene polymorphisms on LDL-C were identified by a generalized multifactor dimensionality reduction (GMDR) approach in 2- to 8-locus models (p<0.05). CONCLUSION: Our results provide evidence that multiple PPARα/δ/γ gene polymorphisms are individually associated with increased LDL-C, and that interactions, among these alleles result in additional increased risk suggesting that PPAR genes may contribute substantially to the risk of cardiovascular diseases and atherosclerosis.

Effect of obesity on the association between common variations in the PPAR gene and C-reactive protein level 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, inflammation, and atherosclerosis. Our aim was to test the association between ten single nucleotide polymorphisms of PPARs and CRP level, as well as their interaction with overweight/obesity. A sample population of 643 subjects was recruited from the prevention of MetS and multi-metabolic disorders in Jiangsu Province of China Study. The selected SNPs in PPAR α (rs135539, rs4253778, rs1800206), PPAR ß/δ (rs2016520 and rs9794), and PPAR γ (rs10865710, rs1805192, rs709158, rs3856806, and rs4684847) were genotyped. After adjustment for smoking, alcohol consumption, SBP, DBP, TG, and HDL-C, rs1800206, rs709158, rs1805192, and rs4684847 polymorphisms were significantly associated with CRP level in normal weight subjects (P < 0.05). In the overweight/obese subjects, rs1800206 was also significant associated with CRP level (P<0.01). In addition, the rs709158, rs1805192, and rs4684847 polymorphisms were shown interactions with overweight/obesity to influence CRP level (P<0.05). PPARs polymorphisms are independently associated with CRP levels in Chinese Han population. Further, PPARs polymorphisms interact with overweight/obesity to set CRP levels.

Peroxisome proliferator­activated receptor γ polymorphisms as risk factors for dyslipidemia.

Peroxisome proliferator­activated receptor Î³ (PPARγ) may play an important role in lipid metabolism directly or by inducing the transcription of target genes. The aim of the present study was to investigate the association between common variants at the PPARγ locus (C1431T and Pro12Ala polymorphisms) and lipid serum levels. The studied population consisted of 820 subjects randomly selected from the Prevention of Multiple Metabolic Disorders and Metabolic Syndrome in Jiangsu Province cohort population. All subjects were interviewed and blood samples were obtained for laboratory analysis and DNA extraction. The TaqMan single nucleotide polymorphism genotyping assay was used for polymorphism genotyping. Individual polymorphisms and haplotype data were available for analysis. The 12Ala allele was found to be associated with significantly increased levels of triglyceride (TG) (P<0.01), whilst the 1431T allele was found to be associated with significantly increased levels of TG, total cholesterol (TC) and non­high­density lipoprotein (non­HDL) (P<0.01). When P­C, the most common haplotype, was used as the reference group, the P­T, A­C and A­T haplotypes were found to be associated with significantly increased levels of TG (P<0.01). In addition, the A­T haplotype was shown to be associated with significantly increased levels of TC and non­HDL (P<0.01). In conclusion these results suggest that PPARγ gene variability may increase the risk of dyslipidemia.

[Roles of peroxisome proliferator-activated receptors polymorphisms, haplotypes, levels on C-reactive protein and their interactions with abnormal body weight].

OBJECTIVE: To explore the roles of peroxisome proliferator-activated receptors (PPARs) on the levels of serum C-reactive protein(CRP)and the interactions of PPARs haplotypes with abnormal body weight. METHODS: Subjects(n = 644)were randomly selected from the cohort 'Prevention of Multiple metabolic disorders and Metabolic syndrome in Jiangsu province(PMMJS)' Variance test, t test and lineal regression were used to analyze the associations between PPARs polymorphisms and the levels of CRP. The association between PPARs haplotypes and serum CRP levels as well as the interaction of PPARs haplotypes with abnormal body weight were analyzed, under the SNPStats software. RESULTS: After adjusting for sex, age, blood pressure, cigarette smoking, alcohol drinking and so on, data showed that both rs1800206 and rs9794 were associated with the changes along with the levels of CRP (P < 0.05). After adjusting for the same factors, haplotypes of AVG and CVG in PPARα, CG in PPARd appeared to be associated with the increase (P < 0.05)while haplotypes of CC in PPARδ, CPCAC in PPARγ were associated with the decrease of CRP levels (P < 0.05). Results from the Interaction analysis also noted that the interactions did exist between abnormal body weight and both AVG, CVG in PPARα, and CG in PPARδ. CONCLUSION: PPARs polymorphisms and haplotypes were associated with CRP. Interaction between PPAR a/d and abnormal body weight might contribute to the levels of CRP.

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.

[Association of both peroxisome proliferator-activated receptor, gene-gene interactions and the lipid accumulation product].

OBJECTIVE: To investigate the association of ten single nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptors (PPARα, δ, γ) with lipid accumulation product (LAP) 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 Metabolic Syndrome in Jiangsu province) cohort populations survey in the urban community of Jiangsu province of China. A total of 820 subjects were randomly selected and no individual was related. Ten SNPs (rs135539, rs4253778, rs1800206, rs2016520, rs9794, rs10865710, rs1805192, rs709158, rs3856806 and rs4684847) were selected from the HapMap database, which covered PPARα, PPARδ and PPARγ. A linear regression model was used to analyze the relations between ten SNPs in the PPARs and LAP. Mean difference (Difference) 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, gender, smoking status, occupational physical activity, educational level, high-fat diet as well as low-fiber diet, both rs1800206, s1805192 and rs3856806 were significantly associated with the increased level of LAP. Difference (95% CI) values were 32.47 (22.62-42.31), 12.97 (4.61-21.33) and 12.49 (4.24-20.75). Whereas rs2016520 was significantly associated with the decreased level of LAP. Difference (95%CI) values was -14.67 ( -22.97--6.55). GMDR analysis showed a significant gene-gene interaction among rs135539, rs1800206 of PPARα, rs2016520 of PPARδ and rs10865710, rs3856806, rs709158, rs1805192, rs4684847 of PPARγ for eight-dimension models (P < 0.05), in which prediction accuracy was 0.5902 and cross-validation consistency was 10/10. CONCLUSION: The rs1800206 of PPARα and rs1805192, rs3856806 of PPARγ were significantly associated with the increased level of LAP; rs2016520 of PPARδ was associated with the decreased level of LAP. There was a gene-gene interaction between multiple SNPs.