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51.
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Linkage and interaction of loci on 1q23 and 16q12 may contribute to susceptibility to systemic lupus erythematosus 总被引:3,自引:0,他引:3
Tsao BP Cantor RM Grossman JM Kim SK Strong N Lau CS Chen CJ Shen N Ginzler EM Goldstein R Kalunian KC Arnett FC Wallace DJ Hahn BH 《Arthritis and rheumatism》2002,46(11):2928-2936
OBJECTIVE: Six recent genome scans of different systemic lupus erythematosus (SLE) multiplex family cohorts showed multiple putative susceptibility loci. In the present study, we examined 4 previously identified loci to replicate findings of significant linkage to 1q23 and 16q12, and to support findings of suggestive linkage to 14q21-23 and 20p12 in a cohort of 115 multiethnic nuclear families containing 145 SLE-affected sibpairs. METHODS: Model-free, multipoint linkage analyses (SIBPAL2, SAGE version 4.0) and exclusion mapping (GeneHunter) were performed. RESULTS: Linkages to 1q23 (peak at D1S2675, mean allele sharing [MAS] 0.56; P = 0.003) and to 16q12 (peaks between D16S753 and D16S757, MAS 0.57; P = 0.003) were confirmed, but linkage evidence at 20p12 was weak and inconsistent (MAS 0.52-0.56; from P = 0.005 to P not significant). Evidence for linkage to 1q23 and 16q12 was stronger in 68 non-Caucasian affected sibpairs than in 77 Caucasian affected sibpairs. Exclusion mapping ruled out linkage at 14q21-23 (lambda(s) [sib recurrence risk or genotypic risk ratio] = 1.8). Because the pericentromeric region of chromosome 16 has been identified by genome scans in several autoimmune diseases, we postulated that it might harbor an autoimmune modifier gene. To explore this possibility, we tested for an interaction between 16q12 and 1q23, and between 16q12 and 20p12. Haplotype sharing at 1q23 increased concomitantly with increased haplotype sharing at 16q12 (P = 0.008 by nonparametric Jonckheere-Terpstra exact statistical test). No evidence supporting an interaction between 16q12 and 20p12 was observed. Analysis of sibpairs sharing 2 alleles at 16q12 also showed increased allele sharing at 1q23 (MAS from 0.56 to 0.65). CONCLUSION: These data support the presence of SLE susceptibility genes at 1q23 and 16q12, particularly in non-Caucasians. The skewed distribution of haplotypes suggests that genetic interaction of these two loci may affect SLE susceptibility. 相似文献
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Regulation of bone cell function by acid-base balance 总被引:8,自引:0,他引:8
Arnett T 《The Proceedings of the Nutrition Society》2003,62(2):511-520
Bone growth and turnover results from the coordinated activities of two key cell types. Bone matrix is deposited and mineralised by osteoblasts and it is resorbed by osteoclasts, multinucleate cells that excavate pits on bone surfaces. It has been known since the early 20th century that systemic acidosis causes depletion of the skeleton, an effect assumed to result from physico-chemical dissolution of bone mineral. However, our own work has shown that resorption pit formation by cultured osteoclasts was absolutely dependent on extracellular acidification; these cells are inactive at pH levels above about 7.3 and show maximum stimulation at a pH of about 6.9. Bone resorption is most sensitive to changes in H+ concentration at a pH of about 7.1 (which may be close to the interstitial pH in bone). In this region pH shifts of < 0.05 units can cause a doubling or halving of pit formation. In whole-bone cultures, chronic HCO3- acidosis results in similar stimulations of osteoclast-mediated Ca2+ release, with a negligible physico-chemical component. In vivo, severe systemic acidosis (pH change of about -0.05 to -0.20) often results from renal disease; milder chronic acidosis (pH change of about -0.02 to -0.05) can be caused by excessive protein intake, acid feeding, prolonged exercise, ageing, airway diseases or the menopause. Acidosis can also occur locally as a result of inflammation, infection, wounds, tumours or diabetic ischaemia. Cell function, including that of osteoblasts, is normally impaired by acid; the unusual stimulatory effect of acid on osteoclasts may represent a primitive 'fail-safe' that evolved with terrestrial vertebrates to correct systemic acidosis by ensuring release of alkaline bone mineral when the lungs and kidneys are unable to remove sufficient H+ equivalent. The present results suggest that even subtle chronic acidosis could be sufficient to cause appreciable bone loss over time. 相似文献
56.
Juhaeri Stevens J Chambless LE Nieto FJ Jones D Schreiner P Arnett D Cai J 《Preventive medicine》2003,36(3):330-339
BACKGROUND: To examine associations of weight loss and changes in fat distribution with changes in blood pressure and the remission of hypertension in a community-based sample. METHODS: Participants were 3245 white and African-American men and women, 45-64 years of age, who participated in the Atherosclerosis Risk in Communities Study over an average of 9 years. Mixed models analyses were used to examine the associations of weight loss and changes in fat distribution with changes in blood pressure. Proportional hazard models with time-dependent covariates were used to examine the associations of weight loss and changes in fat distribution with the remission of hypertension. RESULTS: Weight loss was associated with a decrease in systolic blood pressure and diastolic blood pressure and with an increased rate of remission of hypertension. Hazard ratios of the remission of hypertension associated with 1-kg increment in annual weight loss were 2.04 (95% confidence interval [CI]: 1.62-2.59), 1.38 (95% CI: 1.14-1.67), 1.84 (95% CI: 1.47-2.29), and 1.53 (95% CI: 1.14-2.05) for white women, African-American women, white men, and African-American men, respectively. Changes in fat distribution were associated with the remission of hypertension in younger (45-54 years) participants. CONCLUSIONS: Weight loss was associated with a decrease in blood pressure and with remission of hypertension in white and African-American men and women. 相似文献
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de Simone G Devereux RB Palmieri V Bella JN Oberman A Kitzman DW Hopkins PN Rao DC Arnett DK;HyperGEN Study 《Journal of hypertension》2003,21(9):1747-1752
OBJECTIVES: To evaluate the differences between using height(2.7) or fat-free mass for assessment of the appropriateness of left ventricular mass (LVM) in relation to hemodynamic load, and to evaluate the performance of Doppler as compared with M-mode-derived stroke volume for computation of predicted values of LVM. DESIGN: Cross-sectional. SETTING: Population-based. PARTICIPANTS: We studied 2299 participants from the Hypertension Genetic Epidemiology Network Study (prevalent cardiovascular disease in 342). OUTCOME MEASURES: Individual predicted values of LVM were generated by equations using sex, stroke work (systolic blood pressure x stroke volume by either Doppler or M-mode) and either height(2.7) or fat-free mass, as measures of body build, in 228 normotensive, non-obese, non-diabetic participants. Observed LVM was divided by the predicted value and evaluated as 'excess of LVM'. RESULTS: Among 1957 participants without prevalent cardiovascular disease, obese individuals (n = 1008) were slightly younger than non-obese individuals, whereas diabetic participants (n = 294) were slightly older. Excess of LVM was positively related to body mass index (BMI), independently of echocardiographic method and measure of body build, especially when height(2.7) and m-mode stroke work were used, and was greatest in the presence of concentric left ventricular hypertrophy (P < 0.0001). Excess LVM by height(2.7) was progressively greater than that by fat-free mass, as BMI increased (P < 0.0001). In analyses of covariance of association of prevalent cardiovascular disease with age, sex, race, BMI, and excess of LVM (by each method), methods using height(2.7) were more associated with prevalent cardiovascular disease than were methods using fat-free mass (P < 0.02). CONCLUSIONS: Deviation of LVM from values that compensate hemodynamic load can be similarly identified using different measures of body build and methods to generate stroke work. However, the use of height(2.7) to compute LVM as a percentage of that predicted appears to identify deviations from compensatory values that are independently related to prevalent cardiovascular disease more effectively than does the use of fat-free mass. 相似文献
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Qingxue Wang Judy FC Chow William SB Yeung Estella YL Lau Vivian CY Lee Ernest HY Ng Pak-Chung Ho 《Journal of assisted reproduction and genetics》2014,31(12):1719-1726