Biomedical subjects

Xiping Xu

Publications and source records attributed to Xiping Xu.

At least 55 records · Page 3Linked to original sources

PubMed2004

A candidate gene association study on preterm delivery: application of high-throughput genotyping technology and advanced statistical methods.

Preterm delivery (PTD) is the leading cause of infant mortality and morbidity worldwide. The etiology of PTD is largely unknown but is believed to be complex, encompassing multiple genetic and environmental determinants. To date, reports of genetic studies on PTD are sparse. We conducted a large-scale case-control study exploring the associations of 426 single-nucleotide polymorphisms with PTD in 300 mothers with PTD and 458 mothers with term deliveries at the Boston Medical Center. Twenty-five candidate genes were included in the final haplotype analysis, and a significant association of F5 gene haplotype with PTD was revealed and remained significant after Bonferroni correction for multiple testing (P=0.025). We applied different statistical algorithms (both Gibbs sampling and expectation-maximization) in reconstructing haplotype phases and different tests (both likelihood ratio test and permutation test) in association analyses, and all yielded similar results. We also performed exploratory ethnicity-specific analyses, which confirmed the consistent findings of the F5 gene across the ethnic groups. Moreover, IL1R2 (P=0.002 in Blacks), NOS2A (P<0.001 in Whites) and OPRM1 (P=0.004 in Hispanics) gene haplotypes were associated with PTD in specific ethnic groups but not at global significance level. In summary, our results underscore the potentially important role of F5 gene variants in the pathogenesis of PTD, and demonstrate the utility of high-throughput genotyping and a haplotype-based approach in dissecting genetic basis of complex traits.

Algorithms↗

PubMed2004

Association between the interleukin-1beta C(-511)T polymorphism and blood pressure in a Chinese hypertensive population.

The interleukin-1beta (IL-1beta) is an important pro-inflammatory cytokine in a broad spectrum of physiological processes. Previous investigations have observed that levels of the IL-1beta were higher in essential hypertensive patients and the IL-1beta gene polymorphism has been shown to be related to IL-1 production. We hypothesized that genetically determined differences in activity or responsiveness of cytokine(s) might contribute to hypertension. In this report, we utilized a family-based design to test the association between the IL-1beta C(-511)T polymorphism and blood pressure levels in hypertensive patients chosen from rural communities in Anhui, China. In men, carriers of the IL-1beta (-511)*C allele were found to have lower systolic (P = 0.049) blood pressure levels compared with T homozygotes, which conforms to an additive effect model. By contrast, no significant association between the IL-1beta gene and blood pressure levels was revealed in women. Our results suggested a significant role of the IL-1beta C(-511)T polymorphism in the control of blood pressure in Chinese hypertensives.

Asian People↗

PubMed2004

Power estimation of multiple SNP association test of case-control study and application.

At the current stage, a large number of single nucleotide polymorphisms (SNPs) have been deployed in searching for genes underlying complex diseases. A powerful method is desirable for efficient analysis of SNP data. Recently, a novel method for multiple SNP association test using a combination of allelic association (AA) and Hardy-Weinberg disequilibrium (HWD) has been proposed. However, the power of this test has not been systematically examined. In this study, we conducted a simulation study to further evaluate the statistical power of the new procedure, as well as of the influence of the HWD on its performance. The simulation examined the scenarios of multiple disease SNPs among a candidate pool, assuming different parameters including allele frequencies and risk ratios, dominant, additive, and recessive genetic models, and the existence of gene-gene interactions and linkage disequilibrium (LD). We also evaluated the performance of this test in capturing real disease associated SNPs, when a significant global P value is detected. Our results suggest that this new procedure is more powerful than conventional single-point analyses with correction of multiple testing. However, inclusion of HWD reduces the power under most circumstances. We applied the novel association test procedure to a case-control study of preterm delivery (PTD), examining the effects of 96 candidate gene SNPs concurrently, and detected a global P value of 0.0250 by using Cochran-Armitage chi(2)s as "starting" statistics in the procedure. In the following single point analysis, SNPs on IL1RN, IL1R2, ESR1, Factor 5, and OPRM1 genes were identified as possible risk factors in PTD.

Algorithms↗

PubMed2004

The C677T polymorphism of the methylenetetrahydrofolate reductase gene is associated with the level of decrease on diastolic blood pressure in essential hypertension patients treated by angiotensin-converting enzyme inhibitor.

OBJECTIVES: Elevated plasma homocysteine has been implicated as a risk factor for hypertension. C677T polymorphism in methylenetetrahydrofolate reductase gene (MTHFR) is a major determinant of hyperhomocysteinemia, which results in endothelial dysfunction. Angiotensin-converting enzyme (ACE) inhibitors appear to remedy the endothelial dysfunction and restore endothelium-dependent vasodilatation. The co-existence of genetic polymorphisms in drug metabolizing enzymes, targets, receptors, and transporters may influence the drug efficacy. The purpose of this study was to investigate whether short-term blood pressure control by benazepril, an ACE inhibitor, was modulated by C677T MTHFR gene polymorphism. METHODS AND RESULTS: A total of 444 hypertensive patients, aged 27 to 65 years, without any anti hypertensive therapy within 2 weeks were included. All of them were treated orally with benazepril at a single daily fixed dosage of 10 mg for 15 consecutive days. Blood pressures were measured at baseline and on the 16th day of treatment. Among them, the frequency of MTHFR C677T genotype CC, CT and TT was 24.3%, 51.8%, and 23.9%, respectively. In a recessive model (CC+CT versus TT genotype), both baseline diastolic blood pressure (DBP) and diastolic blood pressure response (DeltaDBP) were significantly higher in patients with the TT genotype than in those with the CT or CC genotype (P value=0.0076 for DBP, and P value=0.0005 for DeltaDBP). We further divided all patients into three groups based on the tertiles of the DeltaBP distribution. Compared to subjects in the lowest tertile of DeltaDBP, the adjusted relative odds of having the TT genotype among subjects in the highest tertile was 2.6 (95% CI, 1.4 to 4.9). However, baseline systolic blood pressure (SBP) and SBP response did not significantly associate with MTHFR C677T polymorphism. CONCLUSIONS: Our finding suggests that MTHFR C667T polymorphism modulated baseline DBP and DBP responsiveness by short-term treatment of ACE inhibitor in Chinese essential hypertensive patients.

Adult↗

PubMed2004

Hypertensive patients from two rural Chinese counties respond differently to benazepril: the Anhui Hypertension Health Care Study.

PURPOSE: Essential hypertension, as a complex disorder with unknown etiology cause, is a major public health problem worldwide. Patients need constant drug therapy to maintain their blood pressure in a normal range. However, the current facts suggest that the treatment is not optimized in a large number of patients, and as a result they are at risk for compliance resulting in uncontrolled blood pressure. Genetic and environmental factors associated with individual variation in response to anti-hypertensive drug remain largely unknown. METHODS: In order to illustrate the existence and to attempt to identify the factors modifying drug effect, we conducted a large-scale follow-up study in two Chinese rural counties differing in both genetic background and residential environment. Hypertensive patients were treated with benazepril, a commonly used angiotensin converting enzyme inhibitor, for 15 days, and the end-point effect was evaluated. RESULTS: We found that there were large and significant differences in drug response between subjects from two counties, even after adjustment for known factors. The responses to benazepril, measured in diastolic blood pressure drop, in male patients from Yuexi was twice as effective as their counterparts from Huoqiu. CONCLUSIONS: These results suggest that adjustment of treatment regimen is necessary to improve efficacy, and it could be done at the population level to make it more feasible and affordable.

Adult↗

PubMed2004

beta(3) Adrenergic receptor polymorphism and obesity-related phenotypes in hypertensive patients.

OBJECTIVES: Obesity is a complex trait that is affected by both environmental and genetic risk factors. The beta(3) adrenergic receptor (ADRB3) is expressed in adipose tissue and plays a role in energy metabolism. A missense mutation on codon 64 of this gene (W64R) is associated with receptor malfunction. Previous studies examining the relation between this polymorphism and obesity produced inconsistent findings. The current study assessed the association between the W64R genotype and obesity-related phenotypes, including body weight, BMI, and serum triglycerides, cholesterol, and glucose. RESEARCH METHODS AND PROCEDURES: We determined the ADRB3 W64R genotypes and fasting serum lipid and glucose concentrations for 695 hypertensive adults (336 men,359 women) from a rural county in Anhui Province, China. Multivariate linear regression models were fit to detect associations between the genetic polymorphism and obesity-related phenotypes. RESULTS: The ADRB3 W64R polymorphism was significantly associated with body weight and BMI in men but not in women. After controlling for potential confounding variables, men who were homozygous for the R64 allele were 11.8 kg heavier (p < 0.001) and had a BMI that was 3.7 kg/m(2) greater (p = 0.001) than men who were homozygous for the W64 allele. Serum concentrations of lipids and glucose were found not associated with the genetic polymorphism. DISCUSSION: The ADRB3 R64 allele was associated with increased body weight and BMI in men but not in women. The genetic association was not modified by triglyceride, cholesterol, blood glucose, or blood pressure levels of the subjects.

Adult↗

PubMed2004

Beta2 adrenergic receptor gene Arg16Gly polymorphism is associated with therapeutic efficacy of benazepril on essential hypertension in Chinese.

BACKGROUND: There is considerable variability in individual response to antihypertensive agents. The reason for this is not known, but may be related to individual genetic variability. This study examined whether the therapeutic efficacy of benazepril on essential hypertension is modified by beta2 adrenergic receptor gene (ADRB2) Arg16Gly (R16G) polymorphism. METHODS AND RESULTS: We conducted a family-based study of 321 and 610 hypertensive subjects from Yuexi and Huoqiu Counties of Anhui, China, respectively. Both systolic and diastolic blood pressures (SBP and DBP) before and after a 15-day benazepril treatment were measured. ADRB2 R16G genotypes were determined for all subjects. ADRB2 G16 allele frequency was found to be 41.0% and. 47.4% in Huoqiu and Yuexi, respectively. In Yuexi family-based association test (FBAT) revealed that the G16 allele was associated with a greater DBP decrease in response to a 15-day benazepril treatment (Z = 2.12, P = 0.03), and the data were consistent with a dominant inheritance model. A similar trend was observed in Huoqiu Chinese, but the magnitudes of effects were smaller and did not reach statistical significance. The FBAT results were further confirmed by using a generalized estimating equation model. CONCLUSION: Our family-based study provided the first evidence that ADRB2 R16G polymorphism may play an important role in DBP response to benazepril treatment, although the magnitude of the effect appears to be modified by other risk factors such as plasma lipid and glucose profiles.

Adult↗

PubMed2004

Preconception hemoglobin and ferritin concentrations are associated with pregnancy outcome in a prospective cohort of Chinese women.

Prenatal anemia and iron deficiency are associated with adverse birth outcomes, but no previous studies have examined the relation between preconception anemia, iron deficiency, and pregnancy outcome in healthy women. We measured hemoglobin (Hb), ferritin, transferrin receptor (TfR), and vitamins B-6, B-12, and folate concentrations before pregnancy in 405 Chinese women (median time from sample collection to gestation end = 316 d). Both mild (95 </= Hb < 120 g/L) and moderate (Hb < 95 g/L) anemia were significantly associated with lower birthweight (139 and 192 g, respectively); iron-deficiency anemia alone (Hb < 120 g, ferritin < 12 microg/L, no B-vitamin deficiency) was associated with a 242-g decrease in birthweight. Both low (<12 microg/L) and high (>/=60 microg/L) ferritin were also significantly associated with lower birthweight (106 and 123 g, respectively). The risks of low birthweight (LBW) and fetal growth restriction (FGR) were significantly greater among women with moderate anemia compared with nonanemic controls [odds ratio (OR): 6.5; 95% CI: 1.6, 26.7; P = 0.009 and OR: 4.6; 95% CI: 1.5, 13.5; P = 0.006, respectively]. TfR and low ferritin were not associated with adverse birth outcome, but elevated ferritin, which could be a marker of inflammation, was associated with increased risk of LBW (OR: 2.2; 95% CI: 0.9, 5.7; P = 0.09) and FGR (OR: 2.7; 95% CI: 1.3, 5.6; P = 0.008). Preconception anemia, particularly iron-deficiency anemia, was associated with reduced infant growth and increased risk of adverse pregnancy outcome in Chinese women.

Adult↗

PubMed2003

Association between polymorphism of the dopamine transporter gene and early smoking onset: an interaction risk on nicotine dependence.

Previous studies suggested that a polymorphism in the dopamine transporter gene (SLC6A3) is associated with nicotine dependence and age of smoking onset, but the conclusion was controversial. To detect the association of a G-->A polymorphism (NCBI dbSNP cluster ID: rs27072) in 3'-untranslated region of the SLC6A3 with nicotine dependence and early smoking onset, we recruited 253 sibships including 668 nicotine-dependent siblings from a rural district of China. The sibship disequilibrium tests (SDT) showed that the rs27072-A allele is significantly associated with smoking onset < or =18 years (kappa2=9.78, p=0.003 in severely nicotine-dependent smokers, and kappa2=4.24, p=0.058 in total smokers), but not significantly associated with severe nicotine dependence. Conditional logistic regression showed that the risk of early smoking onset by the rs27072-A allele was almost three times greater in severely nicotine-dependent smokers [Odds ratio (OR)=11.3, 95% confidence interval (CI)=1.5-85.6] than that in total smokers. Linear regression showed that rs27072-A allele also increased the risk of nicotine dependence by early smoking onset compared with homozygous rs27072-G genotype. Although these findings are preliminary and need validation, the results suggest that a polymorphism in the SLC6A3 may play important roles in smoking onset, and there may be an interactive effect between the SLC6A3 and early smoking onset on modulating the susceptibility of nicotine dependence.

Age of Onset↗

PubMed2003

Low preconception body mass index is associated with birth outcome in a prospective cohort of Chinese women.

Low maternal prepregnancy BMI is associated with adverse birth outcomes, but the BMI at which risk increases is not well defined. We assessed whether the relationship between prepregnancy BMI and birth outcomes is influenced by the extent to which mothers were underweight in a prospective study in Anhui, China. The women (n = 575) were 20-34 y old, married, nulliparous and nonsmokers. All measures of infant growth increased with increasing maternal BMI until a plateau was reached at a BMI of 22-23 kg/m2. Infants born to the 27% of women who were severely underweight before pregnancy (BMI < or = 18.5 kg/m2) were at increased risk for fetal growth deficits associated with infant morbidity. Compared with a normal BMI, being severely underweight was associated with mean (+/- SEM) reductions of 219 +/- 40 g in infant birthweight and 6.7 +/- 1.3% in the birthweight ratio and an 80% increase in risk of intrauterine growth restriction [odds ratio (OR) 1.8; 95% CI: 1.0, 3.3; P = 0.05]. Being severely underweight was also associated with smaller infant head circumference and lower ponderal index. Being moderately underweight (18.5 < BMI < 19.8 kg/m2) was not significantly associated with adverse pregnancy outcomes. Gestational age and risk of preterm birth were not associated with maternal BMI. More than half of the women in this study were underweight before pregnancy. Although being moderately underweight was not associated with increased risk of adverse pregnancy outcomes, being severely underweight was an important risk factor for reduced fetal growth.

Adult↗

PubMed2003

Particulate matter, sulfur dioxide, and daily mortality in Chongqing, China.

In 1995, daily mortality in a district of Chongqing, China, was analyzed from January through December for associations with daily ambient sulfur dioxide and fine particles (airborne particles with diameters less than or equal to 2.5 microm; PM2.5. The mean concentration of PM2.5 was 147 microg/m3 (maximum, 666 microg/m3), and that of SO2 was 213 microg/m3 (maximum, 571 microg/m3). On average, 9.6 persons died each day. We used a generalized additive model using robust Poisson regression to estimate the associations of mean daily SO2 and PM2.5 with daily mortality (on the same day and at lags up to 5 days) adjusted for trend, season, temperature, humidity, and day of the week. The relative risk of mortality associated with a 100 microg/m3 increase in mean daily SO2 was highest on the second lag day [1.04; 95% confidence interval (CI), 1.00-1.09] and the third lag day (1.04; 95% CI, 0.99-1.08). The associations between daily mortality and mean daily PM2.5 were negative and statistically insignificant on all days. The relative risk of respiratory mortality on the second day after a 100 microg/m3 increase in mean daily SO2 was 1.11 (95% CI, 1.02-1.22), and that for cardiovascular mortality was 1.10 (95% CI, 1.02-1.20). The relative risk of cardiovascular mortality on the third day after a 100 microg/m3 increase in mean daily SO2 was 1.20 (95% CI, 1.11-1.30). The relative risks of mortality due to cancer and other causes were insignificant on both days. The estimated effects of mean daily SO2 on cardiovascular and respiratory mortality risk remained after controlling for PM2.5.

Adolescent↗

PubMed2003

Bone resorption is affected by follicular phase length in female rotating shift workers.

Stressors as subtle as night work or shift work can lead to irregular menstrual cycles, and changes in reproductive hormone profiles can adversely affect bone health. This study was conducted to determine if stresses associated with the disruption of regular work schedule can induce alterations in ovarian function which, in turn, are associated with transient bone resorption. Urine samples from 12 rotating shift workers from a textile mill in Anqing, China, were collected in 1996-1998 during pairs of sequential menstrual cycles, of which one was longer than the other (28.4 vs. 37.4 days). Longer cycles were characterized by a prolonged follicular phase. Work schedules during the luteal-follicular phase transition (LFPT) preceding each of the two cycles were evaluated. All but one of the shorter cycles were associated with regular, forward phase work shift progression during the preceding LFPT. In contrast, five longer cycles were preceded by a work shift interrupted either by an irregular shift or a number of "off days." Urinary follicle-stimulating hormone levels were reduced in the LFPT preceding longer cycles compared with those in the LFPT preceding shorter cycles. There was greater bone resorption in the follicular phase of longer cycles than in that of shorter cycles, as measured by urinary deoxypyridinoline. These data confirm reports that changes in work shift can lead to irregularity in menstrual cycle length. In addition, these data indicate that there may be an association between accelerated bone resorption in menstrual cycles and changes of regularity in work schedule during the preceding LFPT.

Adult↗

PubMed2002

[Association of estrogen receptor gene polymorphism with cerebral infarction, a case-control study].

OBJECTIVE: To explore the association between estrogen receptor (ER) gene PvuII and XbaI polymorphisms and cerebral infarction among Chinese Han people. METHODS: Samples of peripheral blood white cell were extracted among 234 patients with cerebral infarction, aged 63.9 +/- 10.3, and 259 controls without cerebrovascular disease, aged 59.2 +/- 9.2, all of Chinese Han nationality. PCR-RFLP and genotyping of ER PvuII and XbaI polymorphisms were performed. Multiple Logistic regression analysis was made to explore the risk factors for cerebral infarction. RESULTS: After adjustment for major confounders including age, gender, smoking, alcohol drinking, education, history of hypertension, diabetes mellitus, coronary artery disease and hyperlipoidemia, multiple Logistic regression analysis showed that: (1) The Pp genotype of ER PvuII polymorphism increased the risk of cerebral infarction significantly (OR = 1.97, 95% CI: 1.21 - 3.21); (2) The ER XbaI polymorphism was not in association with cerebral infarction significantly; (3) The PPXx/Ppxx genotypes increased the risk of cerebral infarction significantly (OR = 1.67, 2.52 and 2.18 respectively, P < 0.05) before or after all subjects were stratified by the history of hypertension or hyperlipoidemia; and (4) The positive interaction between the ER PvuII polymorphism and the presence of hypertension or diabetes or hyperlipoidemia could increase the risk of cerebral infarction significantly. CONCLUSION: ER gene may be one of the genetic candidate genes for cerebral infarction among Chinese Han population.

Aged↗

PubMed2002