RESUMO
BACKGROUND AND OBJECTIVE: Genetic markers associated with disease are often non-functional and generally tag one or more functional "causative" variants in linkage disequilibrium. Markers may not show tight linkage to the causative variants across multiple ethnicities due to evolutionary divergence, and therefore may not be informative across different population groups. Validated markers of disease suggest causative variants exist in the gene and, if the causative variants can be identified, it is reasonable to hypothesize that such variants will be informative across diverse populations. The aim of this study was to test that hypothesis using functional Interleukin-1 (IL-1) gene variations across multiple ethnic populations to replace the non-functional markers originally associated with chronic adult periodontitis in Caucasians. MATERIAL AND METHODS: Adult chronic periodontitis cases and controls from four ethnic groups (Caucasians, African Americans, Hispanics and Asians) were recruited in the USA, Chile and China. Genotypes of IL1B gene single nucleotide polymorphisms (SNPs), including three functional SNPs (rs16944, rs1143623, rs4848306) in the promoter and one intronic SNP (rs1143633), were determined using a single base extension method or TaqMan 5' nuclease assay. Logistic regression and other statistical analyses were used to examine the association between moderate to severe periodontitis and IL1B gene variations, including SNPs, haplotypes and composite genotypes. Genotype patterns associated with disease in the discovery study were then evaluated in independent validation studies. RESULTS: Significant associations were identified in the discovery study, consisting of Caucasians and African Americans, between moderate to severe adult chronic periodontitis and functional variations in the IL1B gene, including a pattern of four IL1B SNPs (OR = 1.87, p < 0.0001). The association between the disease and this IL1B composite genotype pattern was validated in two additional studies consisting of Hispanics (OR = 1.95, p = 0.04) or Asians (OR = 3.27, p = 0.01). A meta-analysis of the three populations supported the association between the IL-1 genotype pattern and moderate to severe periodontitis (OR 1.95; p < 0.001). Our analysis also demonstrated that IL1B gene variations had added value to conventional risk factors in predicting chronic periodontitis. CONCLUSION: This study validated the influence of IL-1 genetic factors on the severity of chronic periodontitis in four different ethnicities.
Assuntos
Periodontite Crônica/imunologia , Etnicidade/genética , Variação Genética/genética , Interleucina-1beta/genética , Adulto , Negro ou Afro-Americano/genética , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , Chile/etnologia , China/etnologia , Periodontite Crônica/genética , Estudos de Coortes , Feminino , Genótipo , Haplótipos/genética , Hispânico ou Latino/genética , Humanos , Indígenas Sul-Americanos/genética , Íntrons/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Estados Unidos/etnologia , População Branca/genéticaRESUMO
OBJECTIVE: This study evaluated the relationship between periodontal disease and low birth weight (LBW) in a predominantly black population. METHODS: Using the nested case-control design, we evaluated the periodontal pathogen specific maternal serum IgG levels during pregnancy in relation to birth weight, while controlling for the known risk factors for LBW. RESULTS: There was a significant negative correlation (r= -0.37; p= 0.004) between the birth rate of the infant and Porphyromonas gingivalis (Pg) specific maternal serum IgG levels (LBW group - mean/SE 14.73ñ4.67 ug/ml; p= 0.003). Regression analysis indicated that one unit increase of IgG against Pg in the mother resulted in 5.07g decrease in the birth weight of the infant (p=0.005). CONCLUSION: Our ability to demonstrate a significant difference in the serum IgG levels, against at least one periodontal pathogen (Pg) lends further credibility to the biologic plausibility of the association between poor periodontal health and LBW, and the temporal sequence of this association. (AU)
Assuntos
Lactente , Adulto , Feminino , Humanos , Doenças Periodontais , Recém-Nascido de Baixo Peso , Estudos de Casos e Controles , Negro ou Afro-AmericanoRESUMO
BACKGROUND: Type 2 diabetes mellitus and atherosclerotic cardiovascular disease have common antecedents. Since markers of inflammation predict coronary heart disease and are raised in patients with type 2 diabetes, we investigated whether they predict whether people will develop type 2 diabetes. METHODS: 12,330 men and women, aged 45-64 years, were followed up for a mean of 7 years. We analysed the association between different markers of acute inflammation and subsequent diagnosis of diabetes. In a subgroup of 610 individuals selected originally for an unrelated atherosclerosis case-control study, we also investigated diabetes associations with total sialic acid and orosomucoid, haptoglobin, and alpha1-antitrypsin. FINDINGS: 1335 individuals had a new diagnosis of diabetes. Adjusted odds ratios for developing diabetes for quartile extremes were 1.9 (95% CI 1.6-2.3) for raised white-cell count, 1.3 (1.0-1.5) for low serum albumin, and 1.2 (1.0-1.5) for raised fibrinogen. In the subgroup analysis, individuals with concentrations of orosomucoid and sialic acid of more than the median had odds ratios of 7.9 (2.6-23.7) and 3.7 (1.4-9.8), respectively. Adjustment for body-mass index and waist-to-hip ratio lessened the associations; those for white-cell count (1.5 [1.3-1.8]), orosomucoid (7.1 [2.1-23.7]), and sialic acid (2.8 [1.0-8.1]) remained significant. INTERPRETATION: Markers of inflammation are associated with the development of diabetes in middle-aged adults. Although autoimmunity may partly explain these associations, they probably reflect the pathogenesis of type 2 diabetes.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Autoimunidade , Biomarcadores , Estudos de Coortes , Diabetes Mellitus Tipo 2/imunologia , Feminino , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Orosomucoide/análise , Prognóstico , Fatores de Risco , Ácidos Siálicos/sangueRESUMO
OBJECTIVE: Our objective was to evaluate whether selected hemostasis variables, some of which may reflect inflammation or endothelial dysfunction, are independently associated with the development of diabetes. RESEARCH DESIGN AND METHODS: We studied a biethnic cohort of 12,330 men and women, 45-64 years of age, of the Atherosclerosis Risk in Communities Study. New cases of diabetes were diagnosed by a reported physician diagnosis, hypoglycemic medication use, or a casual or fasting serum glucose level of > or = 11.1 or > or = 7 mmol/l, respectively. RESULTS: Over an average follow-up of 7 years, 1,335 new cases of diabetes were detected. The odds ratios (4th versus 1st quartile) of developing diabetes, adjusted by logistic regression for age, sex, race, study center, family history of diabetes, fasting glucose, physical activity, and smoking, were 1.2 (95% CI 1.0-1.5) for fibrinogen and 1.4 (1.1-1.6) for factor VII. Associations for factor VIII, von Willebrand factor, and activated partial thromboplastin time were found to be 1.8 (1.3-2.3), 1.4 (1.1-1.8), and 0.63 (0.49-0.82), respectively, in women. Although further adjustment for BMI and waist-to-hip ratio diminished the relationships, a highly statistically significant association (P = 0.001) remained for factor VIII (1.6 [1.2-2.1]) in women. CONCLUSIONS: Factor VIII and other hemostasis variables are associated with the development of diabetes in middle-aged adults. These findings support a role for inflammation and, particularly in women, endothelial dysfunction in the pathogenesis of type 2 diabetes.