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NCK2 is significantly associated with opiates addiction in African-origin men.

ABSTRACT: Substance dependence is a complex environmental and genetic disorder with significant social and medical concerns. Understanding the etiology of substance dependence is imperative to the development of effective treatment and prevention strategies. To this end, substantial effort has been made to identify genes underlying substance dependence, and in recent years, genome-wide association studies (GWASs) have led to discoveries of numerous genetic variants for complex diseases including substance dependence. Most of the GWAS discoveries were only based on single nucleotide polymorphisms (SNPs) and a single dichotomized outcome. By employing both SNP- and gene-based methods of analysis, we identified a strong (odds ratio = 13.87) and significant (P value = 1.33E - 11) association of an SNP in the NCK2 gene on chromosome 2 with opiates addiction in African-origin men. Codependence analysis also identified a genome-wide significant association between NCK2 and comorbidity of substance dependence (P value = 3.65E - 08) in African-origin men. Furthermore, we observed that the association between the NCK2 gene (P value = 3.12E - 10) and opiates addiction reached the gene-based genome-wide significant level. In summary, our findings provided the first evidence for the involvement of NCK2 in the susceptibility to opiates addiction and further revealed the racial and gender specificities of its impact.

SUBMITTER: Liu Z

PROVIDER: S-EPMC3603435 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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NCK2 is significantly associated with opiates addiction in African-origin men.

Liu Zhifa Z Guo Xiaobo X Jiang Yuan Y Zhang Heping H

TheScientificWorldJournal 20130228

Substance dependence is a complex environmental and genetic disorder with significant social and medical concerns. Understanding the etiology of substance dependence is imperative to the development of effective treatment and prevention strategies. To this end, substantial effort has been made to identify genes underlying substance dependence, and in recent years, genome-wide association studies (GWASs) have led to discoveries of numerous genetic variants for complex diseases including substance ...[more]

PMID: 23533358

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Project description:BackgroundBlack African (BA) populations are losing the cardio-protective lipid profile they historically exhibited, which may be linked with increasing fructose intakes. The metabolic effects of high fructose diets and how they relate to blood lipids are documented for Caucasians, but have not been described in BA individuals.ObjectiveThe principle objective of this pilot study was to assess the independent impacts of high glucose and fructose feeding in men of BA ancestry compared to men of White European (WE) ancestry on circulating triglyceride (TG) concentrations.MethodsHealthy males, aged 25-60 years, of BA (n = 9) and WE (n = 11) ethnicity were randomly assigned to 2 feeding days in a crossover design, providing mixed nutrient meals with 20 % total daily caloric requirements from either added glucose or fructose. Circulating TG, non-esterified fatty acids (NEFA), glucose, insulin and C-peptide were measured over two 24-h periods.ResultsFasting TGs were lower in BAs than WEs on the fructose feeding day (p < 0.05). There was a trend for fasting TG concentrations 24 h following fructose feeding to increase in both BA (baseline median fasting: 0.80, IQR 0.6-1.1 vs 24-h median post-fructose: 1.09, 0.8-1.4 mmol/L; p = 0.06) and WE (baseline median fasting 1.10, IQR 0.9-1.5 vs 24-h median post-fructose: 1.16, IQR 0.96-1.73 mmol/L; p = 0.06). Analysis within ethnic group demonstrated that in TG iAUC was significantly higher in BA compared to WE on both glucose (35, IQR 11-56 vs -4, IQR -10-1 mmol/L/min; p = 0.004) and fructose (48, IQR 15-68 vs 13, IQR -7-38 mmol/L/min; p = 0.04). Greater suppression of postprandial NEFA was evident in WE than BA after glucose feeding (-73, IQR -81- -52 vs -26, IQR -48- -3 nmol/L/min; p = 0.001) but there was no ethnic difference following fructose feeding.ConclusionsUnderstanding the metabolic effects of dietary acculturation and Westernisation that occurs in Black communities is important for developing prevention strategies for chronic disease development. These data show postprandial hypertriglyceridemia following acute feeding of high added fructose and glucose in BA men, compared to WE men, may contribute to metabolic changes observed during dietary acculturation and Westernisation.Trial registrationThe study was retrospectively registered on clinicaltrials.gov: NCT02533817 .

Dataset Information

NCK2 is significantly associated with opiates addiction in African-origin men.

Publications

NCK2 is significantly associated with opiates addiction in African-origin men.

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