Dataset Information

Positive selection in Europeans and East-Asians at the ABCA12 gene.

ABSTRACT: Natural selection acts on genetic variants by increasing the frequency of alleles responsible for a cellular function that is favorable in a certain environment. In a previous genome-wide scan for positive selection in contemporary humans, we identified a signal of positive selection in European and Asians at the genetic variant rs10180970. The variant is located in the second intron of the ABCA12 gene, which is implicated in the lipid barrier formation and down-regulated by UVB radiation. We studied the signal of selection in the genomic region surrounding rs10180970 in a larger dataset that includes DNA sequences from ancient samples. We also investigated the functional consequences of gene expression of the alleles of rs10180970 and another genetic variant in its proximity in healthy volunteers exposed to similar UV radiation. We confirmed the selection signal and refine its location that extends over 35 kb and includes the first intron, the first two exons and the transcription starting site of ABCA12. We found no obvious effect of rs10180970 alleles on ABCA12 gene expression. We reconstructed the trajectory of the T allele over the last 80,000 years to discover that it was specific to H. sapiens and present in non-Africans 45,000 years ago.

SUBMITTER: Sirica R

PROVIDER: S-EPMC6424970 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Positive selection in Europeans and East-Asians at the ABCA12 gene.

Sirica Roberto R Buonaiuto Marianna M Petrella Valeria V Sticco Lucia L Tramontano Donatella D Antonini Dario D Missero Caterina C Guardiola Ombretta O Andolfi Gennaro G Kumar Heerman H Ayub Qasim Q Xue Yali Y Tyler-Smith Chris C Salvemini Marco M D'Angelo Giovanni G Colonna Vincenza V

Scientific reports 20190319 1

Natural selection acts on genetic variants by increasing the frequency of alleles responsible for a cellular function that is favorable in a certain environment. In a previous genome-wide scan for positive selection in contemporary humans, we identified a signal of positive selection in European and Asians at the genetic variant rs10180970. The variant is located in the second intron of the ABCA12 gene, which is implicated in the lipid barrier formation and down-regulated by UVB radiation. We st ...[more]

PMID: 30890716

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Project description:BACKGROUND:The pathogenesis and cardiovascular impact of type 2 diabetes (T2D) may be different in South Asians compared with other ethnic groups. The phenotypic characterization of diabetic cardiomyopathy remains debated and little is known regarding differences in T2D-related cardiovascular remodeling across ethnicities. We aimed to characterize the differences in left ventricular (LV) diastolic and systolic function, LV structure, myocardial tissue characteristics and aortic stiffness between T2D patients and controls and to assess the differences in T2D-related cardiovascular remodeling between South Asians and Europeans. METHODS:T2D patients and controls of South Asian and European descent underwent 3 Tesla cardiovascular magnetic resonance imaging (CMR) and cardiac proton-magnetic resonance spectroscopy (1H-MRS). Differences in cardiovascular parameters between T2D patients and controls were examined using ANCOVA and were reported as mean (95% CI). Ethnic group comparisons in the association of T2D with cardiovascular remodeling were made by adding the interaction term between ethnicity and diabetes status to the model. RESULTS:A total of 131 individuals were included (54 South Asians [50.1?±?8.7 years, 33% men, 33 patients vs. 21 controls) and 77 Europeans (58.8?±?7.0 years, 56% men, 48 patients vs. 29 controls)]. The ratio of the transmitral early and late peak filling rate (E/A) was lower in T2D patients compared with controls, in South Asians [-?0.20 (-?0.36; -?0.03), P?=?0.021] and Europeans [-?0.20 (-?0.36; -?0.04), P?=?0.017], whereas global longitudinal strain and aortic pulse wave velocity were similar. South Asian T2D patients had a higher LV mass [+?22 g (15; 30), P?<?0.001] (P for interaction by ethnicity?=?0.005) with a lower extracellular volume fraction [-?1.9% (-?3.4; -?0.4), P?=?0.013] (P for interaction?=?0.114), whilst European T2D patients had a higher myocardial triglyceride content [+?0.59% (0.35; 0.84), P?=?0.001] (P for interaction?=?0.002) than their control group. CONCLUSIONS:Diabetic cardiomyopathy was characterized by impaired LV diastolic function in South Asians and Europeans. Increased LV mass was solely observed among South Asian T2D patients, whereas differences in myocardial triglyceride content between T2D patients and controls were only present in the European cohort. The diabetic cardiomyopathy phenotype may differ between subsets of T2D patients, for example across ethnicities, and tailored strategies for T2D management may be required.

Dataset Information

Positive selection in Europeans and East-Asians at the ABCA12 gene.

Publications

Positive selection in Europeans and East-Asians at the ABCA12 gene.

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