In Search of Susceptibility Genes for Type 2 Diabetes in West Africa

Rotimi, Charles N.; Dunston, Georgia M.; Berg, Kate; Akinsete, Omobosola; Amoah, Albert; Owusu, Samuel; Acheampong, Joseph; Boateng, Kwame Osei; Oli, Johnnie; Okafor, Godfrey; Onyenekwe, Belonwu M.; Osotimehin, Babatunde; Abbiyesuku, F M; Johnson, Thomas; Fasanmade, O.A; Furbert-Harris, Paulette; Kittles, Rick A.; Vekich, Mirjana; Adegoke, Olufemi; Bonney, George E.; Collins, Francis S.

doi:10.1016/s1047-2797(00)00180-0

Cited by 77 publications

(30 citation statements)

References 20 publications

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“…There is a strong evidence to suggest insulin resistance is genetically determined with a strong familial and environmental component [33,34,35,36,37]. Insulin resistance has a predilection for certain ethnic groups [13,16,17,24,36,37].…”

Section: Discussionmentioning

confidence: 99%

Insulin sensitivity and cardiovascular risk factors in hypertensive and normotensive native Ghanaians

et al. 2003

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Aims/Hypothesis. The objective of this study was to examine the relationships among insulin and insulin sensitivity and risk factors for cardiovascular diseases in native Ghanaians with and without hypertension. Methods. We measured the anthropometric parameters, systolic and diastolic blood pressure, fasting serum triglycerides, cholesterol and high-density lipoprotein cholesterol and fasting and stimulated glucose, insulin and C-peptide of 200 Ghanaian subjects, who were between 25 to 74 years of age, and residing in the Accra Metropolitan area. Serum glucose, C-peptide and insulin concentrations were measured at baseline (fasting) and also 2 h after 75 gm oral glucose drink. Homeostasis model assessment was used to measure insulin resistance. Hypertension was defined as a blood pressure higher than 140/90 mmHg.Results. There were 53 subjects with hypertension (HBP) and 147 subjects with normal blood pressure (NBP). The mean BMI, waist circumference and waist-to-hip circumference ratio for HBP and NBP subjects were 27.4±0.8, 24.8±0.4 kg/m 2 ; 89.8±11.7, 81.1±0.9 cm; and 0.87±0.08, 0.82±0.08 respectively, (p<0.05). The fasting and 2-h plasma glucose concentrations in HBP and NBP subjects were 5.5±0.2, 7.2±0.3 mmol/l and 5.2±01, 6.8±0.2 mmol/l respectively (p>0.05). The corresponding fasting and 2-h insulin concentrations were 10.0±0.7, 8.0±0.4 uU/ml and 47.3±3.7, 37.3±2.5 uU/ml respectively (p<0.05). The insulin resistance index (HOMA-IR) in the HBP and the NBP groups were 2.49±0.2 and 1.95±0.13 (p<0.05). The two groups had similar fasting and stimulated C-peptide, lipids and HDL concentrations. Correlations were found between blood pressure and the concentrations of lipids, HDL, fasting and stimulated insulin and C-peptide, and between fasting insulin and HOMA-IR with lipids and HDL concentrations. On multiple regression analysis, fasting insulin and HOMA-IR did not influence blood pressure variations significantly. Conclusions/interpretation. We found clustering of hyperinsulinaemia, insulin resistance and truncal obesity in hypertensive Ghanaian subjects but dissociation between insulin resistance, hypertension and atherogenic lipid and lipoprotein profile. [Diabetologia (2003) 46:949-955] Keywords Insulin sensitivity, blood pressure, lipids, lipoproteins, hypertension, ghanaians, insulin resistance.

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Section: Discussionmentioning

confidence: 99%

Insulin sensitivity and cardiovascular risk factors in hypertensive and normotensive native Ghanaians

et al. 2003

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“…Although the AADM study has been ongoing for over a decade, the majority of participants included in the present analysis was recruited in the year 2008. The study populations, data collection procedures, and ethical processes have been described in detail elsewhere [27, 28]. …”

Section: Methodsmentioning

confidence: 99%

Genome-wide association study identifies African-ancestry specific variants for metabolic syndrome

Tekola‐Ayele

Doumatey

Shriner

et al. 2015

Molecular Genetics and Metabolism

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The metabolic syndrome (MetS) is a constellation of metabolic disorders that increase the risk of developing several diseases including type 2 diabetes and cardiovascular diseases. Although genome-wide association studies (GWAS) have successfully identified variants associated with individual traits comprising MetS, the genetic basis and pathophysiological mechanisms underlying the clustering of these traits remain unclear. We conducted GWAS of MetS in 1,427 Africans from Ghana and Nigeria followed by replication testing and meta-analysis in another continental African sample from Kenya. Further replication testing was performed in an African American sample from the Atherosclerosis Risk in Communities (ARIC) study. We found two African-ancestry specific variants that were significantly associated with MetS: SNP rs73989312[A] near CA10 that conferred increased risk (P=3.86x10−8, OR=6.80) and SNP rs77244975[C] in CTNNA3 that conferred protection against MetS (P=1.63x10−8, OR=0.15). Given the exclusive expression of CA10 in the brain, our CA10 finding strengthens previously reported link between brain function and MetS. We also identified two variants that are not African specific: rs76822696[A] near RALYL associated with increased MetS risk (P=7.37x10−9, OR=1.59) and rs7964157[T] near KSR2 associated with reduced MetS risk (P=4.52x10−8, Pmeta=7.82x10−9, OR=0.53). The KSR2 locus displayed pleiotropic associations with triglyceride and measures of blood pressure. Rare KSR2 mutations have been reported to be associated with early onset obesity and insulin resistance. Finally, we replicated the LPL and CETP loci previously found to be associated with MetS in Europeans. These findings provide novel insights into the genetics of MetS in Africans and demonstrate the utility of conducting trans-ethnic disease gene mapping studies for testing the cosmopolitan significance of GWAS signals of cardio-metabolic traits.

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“…The comparison of large datasets of AA and WA designed by the same researcher with data collected using the same questionnaires (with culturally-relevant adjustments) is useful at this point. Characteristics of AA (further description [12]) and WA (further description [13]) is provided, along with similar data on NHANES (further description [14,15]) EA and AA (Table 1). The importance of a lifestyle factor as a key determinant of interethnic differences in serum lipids appears unlikely given the presented data.…”

Section: Why Is There An Interethnic Difference?mentioning

confidence: 99%

Interethnic variation in lipid profiles: implications for underidentification of African–Americans at risk for metabolic disorders

Bentley

Rotimi

2012

Expert Review of Endocrinology & Metabolism

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Summary Interethnic differences exist in the distribution of serum lipids, with African Americans (AA) generally having a healthier lipid profile than other US ethnic groups. Similar lipid distributions are observed among other African ancestry groups with distinct lifestyle characteristics, suggesting the importance of inherited factors. Despite healthier serum lipids, AA experience a disproportionate burden of Type 2 Diabetes and Cardiovascular Disease. As evidence of a different relationship between serum lipids and disease exists, the characterization of metabolic risk using lipid concentration (as in Metabolic Syndrome criteria) may lead to the under-identification of AA at risk. Given the disproportionately high rate of metabolic disorders in AA, understanding interethnic differences in the association between serum lipids and disease should be a research priority, as better appreciation of these differences will enhance knowledge of disease etiology, improve intervention targeting, and may lead to mechanisms to ameliorate debilitating health disparities in the US and globally.

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In Search of Susceptibility Genes for Type 2 Diabetes in West Africa

Cited by 77 publications

References 20 publications

Insulin sensitivity and cardiovascular risk factors in hypertensive and normotensive native Ghanaians

Insulin sensitivity and cardiovascular risk factors in hypertensive and normotensive native Ghanaians

Genome-wide association study identifies African-ancestry specific variants for metabolic syndrome

Interethnic variation in lipid profiles: implications for underidentification of African–Americans at risk for metabolic disorders

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