Relation of type 2 diabetes to individual admixture and candidate gene polymorphisms in the Hispanic American population of San Luis Valley, Colorado

Parra, Esteban J.; Hoggart, Clive; Bonilla, Carolina; Dios, S.; Norris, J. M.; Marshall, Julie A.; Hamman, Richard F.; Ferrell, Robert E.; McKeigue, Paul; Shriver, Mark D.

doi:10.1136/jmg.2004.018887

Cited by 41 publications

(40 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, we did not observe any relationships with diabetesrelated quantitative traits (Table 3). This observation is in contrast with the findings of a study in which the T allele was associated with higher fasting insulin concentrations among 261 non-diabetic Hispanic Americans [52]. In addition, a Polish study (n=344) reported that the T allele was more frequent among type 2 diabetic patients than control subjects [13], and in a study of subjects from the United Arab Emirates (n=510) the TT genotype was overrepresented among type 2 diabetic patients [32].…”

Section: Discussioncontrasting

confidence: 55%

“…Moreover, large disparities in the frequency of the 825T allele between populations of different ethnicities have been observed, ranging from as high as 65-91% among Africans, to 42-52% among Asians and 21-35% in Europeans [36]. Deviations from Hardy-Weinberg equilibrium were also observed in two studies of the GNB3 825C>T polymorphism in type 2 diabetes, one of which suggested that the T allele conferred a significantly increased risk of the disease [31,52]. We genotyped approximately 1% of our DNA samples in duplicate, and this yielded no discrepancies.…”

Section: Discussionmentioning

confidence: 95%

See 1 more Smart Citation

Studies of the association of the GNB3 825C>T polymorphism with components of the metabolic syndrome in white Danes

et al. 2005

View full text Add to dashboard Cite

Aims/hypothesis: The 825C>T polymorphism in the gene encoding the G protein β3 subunit (GNB3) causes enhanced G protein activation and increased in vitro cell proliferation. This polymorphism is also repeatedly associated with an increased risk of hypertension and has been studied in relation to obesity with divergent results. Only a few association studies have investigated whether this polymorphism is related to type 2 diabetes or the metabolic syndrome. We estimated the impact of the GNB3 825C>T polymorphism in relatively large-scale association studies of common phenotypes of the metabolic syndrome. Materials and methods: The GNB3 825C>T polymorphism was genotyped in 7,518 white Danish subjects using mass spectrometry analysis of PCR products. Case-control studies were undertaken for obesity, hypertension, type 2 diabetes and the metabolic syndrome, and a meta-analysis including data from the present study and previous studies of hypertension was performed. Quantitative trait studies of metabolic variables were carried out in 4,387 glucose-tolerant subjects. Results: We observed minor differences in 825C>T genotype distributions for type 2 diabetes (CC/CT/TT 49/41/10% (control) vs 46/46/9% (cases), respectively, p=0.007); however, after correction for multiple testing, these were not statistically significant. No association was found with hypertension, obesity or the metabolic syndrome. Curiously, the T allele was associated with nominally lower systolic and diastolic blood pressure levels-a finding in contrast with most previous studies-but not with other metabolic variables. Meta-analysis demonstrated a high degree of heterogeneity between study populations of different ethnic origin. Although there was a tendency towards an increased risk of hypertension among 825T allele carriers, this was not statistically significant. Conclusions/interpretation: The present study suggests no major involvement of the GNB3 825C>T polymorphism in components of the metabolic syndrome.

show abstract

Section: Discussioncontrasting

confidence: 55%

Section: Discussionmentioning

confidence: 95%

Studies of the association of the GNB3 825C>T polymorphism with components of the metabolic syndrome in white Danes

et al. 2005

View full text Add to dashboard Cite

show abstract

“…Para contrarrestar esto, existe un modelo estadístico que permite ajustar las pruebas de asociación alélica y haplotípica para la mezcla individual como factor de confusión (21,22).…”

unclassified

Asociación de variantes en genes de las proteínas desacoplantes con diabetes mellitus tipo 2 en una población del nordeste colombiano

et al. 2009

View full text Add to dashboard Cite

Introducción. Las proteínas desacoplantes pertenecen a la familia de proteínas transportadoras de aniones que desacoplan la producción de ATP de la respiración mitocondrial, causando pérdida de protones a través de la membrana mitocondrial interna y disipando la energía en forma de calor. Aunque su función no ha sido bien establecida, algunos polimorfismos en estas proteínas se han asociado con diabetes mellitus tipo 2, obesidad y resistencia a la insulina. Objetivo. Evaluar la asociación entre las variantes -3826A/G, ID 45, -2723T/A, -1957G/A, -866G/A, -55C/T de los genes de las proteínas desacoplantes 1, 2 y 3 con diabetes mellitus tipo 2 en una población del nordeste colombiano. Materiales y métodos. Se tipificaron 545 casos y 449 controles para 14 variantes de los genes de las proteínas desacoplantes por medio de PCR y PCR-RFLP. Se hicieron pruebas de asociación simples con ji al cuadrado y se corrigieron en un análisis de regresión logística bayesiana, incluyendo los estimados de mezcla individual obtenidos mediante 54 marcadores informativos de ascendencia europea, africana y amerindia. Resultados. Las variantes -3826A (OR=0,78; IC95% 0,63-0,97; p=0,02), -55C (OR=1,41; IC95% 1,04-1,92; p=0,03) de las proteínas desacoplantes 1 y 3, respectivamente, y el haplotipo D45, -866G, -1957G, -2723T, -55C (OR=1,26; IC95% 1,02-1,56; p=0,03) se asociaron con diabetes tipo 2. Estas asociaciones se conservaron después de ajustar por la mezcla genética individual. Conclusión. Algunas variantes de las proteínas desacoplantes 1, 2 y 3, y sus haplotipos, confieren riesgo para diabetes mellitus tipo 2 en una población del nordeste colombiano.Palabras clave: diabetes mellitus/genética, resistencia a insulina, obesidad, genotipo, haplotipos. Association between polymorphism in uncoupling proteins and type 2 diabetes in a northwestern Colombian populationIntroduction. The uncoupling proteins belong to the family of anion transporting proteins which uncouple the ATP production from the mitochondrial respiration, cause proton leakage through the inner mitochondrial membrane, and release energy as heat. Although uncoupling protein function has not been well established, specific polymorphisms in these proteins have been associated with type 2 diabetes mellitus, obesity and insulin resistance. Objective. The association was assessed between the polymorphisms in uncoupling protein genes 1, 2 and 3 genes and type 2 diabetes mellitus. Materials and methods. In a northwestern Colombian population, 545 diabetes cases and 449 controls were investigated for presence of 14 polymorphisms in uncoupling protein genes (3826A/G, ID 45, 2723T/A, 1957G/A, 866G/A, and 55C/T) by PCR and PCR-RFLP. Single associations were evaluated by chi-square test, and bayesian logistic regression analysis was done including as covariates the individual admixture estimates obtained by 54 D45, 866G, 1957G, 2723T, and 55C (OR=1.26; 95%CI=1.02-1.56; p=0.03) were found. These associations remained after adjustment using individual genetic admixture estimates. Concl...

show abstract

“…Hispanic populations in the U.S. Southwest have genetic heritage from Europeans and from American Indians (1,2), and this background influences their incidence of chronic diseases (3)(4)(5)(6). Age-adjusted breast cancer incidence among non-Hispanic White (i.e., European-American) women in New Mexico is 134.8 per 100,000 per year, about two and a half times higher than the incidence among American Indians, 53.4 per 100,000.…”

Section: Introductionmentioning

confidence: 99%

Genetic Admixture among Hispanics and Candidate Gene Polymorphisms: Potential for Confounding in a Breast Cancer Study?

Sweeney¹,

Wolff²,

Byers

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

Hispanics in the U.S. Southwest have genetic ancestry from Europeans and from American Indians, two groups with markedly different breast cancer incidence rates. Genetic admixture may therefore bias estimates of associations between candidate cancer susceptibility genes and breast cancer in Hispanics. We estimated genetic admixture using 15 ancestry-informative markers for 1,239 Hispanics and 2,505 non-Hispanic Whites in a breast cancer case-control study in the Southwest, the Four Corners Study. Confounding risk ratios (CRR) were calculated to quantify potential bias due to admixture. Genetic admixture was strongly related to selfreported race and ethnic background (P < 0.0001). Among Hispanic controls, admixture was significantly associated with allele frequency for 5 of 11 candidate gene single nucleotide polymorphisms (SNP) examined. Hispanics in the highest versus the lowest quintile of American Indian admixture had higher mean body mass index at age 30 years (25.4 versus 23.6 kg/m 2 ; P = 0.003), shorter mean height (1.56 versus 1.58 m; P = 0.01), higher prevalence of diabetes (14.8% versus 7.2%; P = 0.04), and a larger proportion with less than a high school education (38.5% versus 23.2%; P = 0.001). Admixture was not associated with breast cancer risk among Hispanics (P = 0.65). CRRs for potential bias to candidate SNP-breast cancer risk ratios ranged from 0.99 to 1.01. Thus, although genetic admixture in Hispanics was associated with exposures, confounding by admixture was negligible due to the null association between admixture and breast cancer. CRRs from simulated scenarios indicated that appreciable confounding by admixture would occur only when within-group candidate SNP allele frequency differences are much larger than any that we observed. (Cancer Epidemiol Biomarkers Prev 2007;16(1):142 -50)

show abstract

Relation of type 2 diabetes to individual admixture and candidate gene polymorphisms in the Hispanic American population of San Luis Valley, Colorado

Cited by 41 publications

References 45 publications

Studies of the association of the GNB3 825C>T polymorphism with components of the metabolic syndrome in white Danes

Studies of the association of the GNB3 825C>T polymorphism with components of the metabolic syndrome in white Danes

Asociación de variantes en genes de las proteínas desacoplantes con diabetes mellitus tipo 2 en una población del nordeste colombiano

Genetic Admixture among Hispanics and Candidate Gene Polymorphisms: Potential for Confounding in a Breast Cancer Study?

Contact Info

Product

Resources

About