Effect of six type II diabetes susceptibility loci and an FTO variant on obesity in Pakistani subjects

Shabana, N.A.; Shahid, Saleem Ullah; Li, Ka Wah; Acharya, Jayshree; Hasnain, Shahida; Humphries, S. E.

doi:10.1038/ejhg.2015.212

Cited by 25 publications

(18 citation statements)

References 59 publications

(73 reference statements)

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“…It has been found to affect anticonvulsant response during a seizure test in mice [67]. Mutations in CA8 can cause ataxia [68,69] and mild mental retardation [70] VPS26 plays a role in sensitisation to pain [71] diabetes susceptibility [72] and is involved in trafficking and sorting of transmembrane proteins [73].…”

Section: Discussionmentioning

confidence: 99%

Genetical Genomics of Tonic Immobility in the Chicken

Fogelholm

Inkabi

Höglund

et al. 2019

Genes

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Identifying the molecular mechanisms of animal behaviour is an enduring goal for researchers. Gaining insight into these mechanisms enables us to gain a greater understanding of behaviour and their genetic control. In this paper, we perform Quantitative Trait Loci (QTL) mapping of tonic immobility behaviour in an advanced intercross line between wild and domestic chickens. Genes located within the QTL interval were further investigated using global expression QTL (eQTL) mapping from hypothalamus tissue, as well as causality analysis. This identified five candidate genes, with the genes PRDX4 and ACOT9 emerging as the best supported candidates. In addition, we also investigated the connection between tonic immobility, meat pH and struggling behaviour, as the two candidate genes PRDX4 and ACOT9 have previously been implicated in controlling muscle pH at slaughter. We did not find any phenotypic correlations between tonic immobility, struggling behaviour and muscle pH in a smaller additional cohort, despite these behaviours being repeatable within-test.

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Section: Discussionmentioning

confidence: 99%

Genetical Genomics of Tonic Immobility in the Chicken

Fogelholm

Inkabi

Höglund

et al. 2019

Genes

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“…It was taken care that cases and controls represented all the socioeconomic groups. Subjects with obesity (BMI > 26Kg/m 2 for Asian populations [ 20 ]) were excluded from the study to reduce the possible confouders. Any subject with infection was excluded from the study.…”

Section: Methodsmentioning

confidence: 99%

GWAS implicated risk variants in different genes contribute additively to increase the risk of coronary artery disease (CAD) in the Pakistani subjects

et al. 2018

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BackgroundCoronary artery disease (CAD) remains the single most important cause of mortality worldwide. Many candidate and GWAS genetic variants have been identified in the recent years. In the current study, we selected six SNPs from various genes that have originally been identified in GWAS studies and examined the association of SNPs individually and as a genetic risk score (GRS) with CAD and blood lipid levels in the Pakistani subjects.MethodsSix hundred twenty-four (404 cases and 219 controls) subjects were genotyped for variants rs10757274 in CDKN2A gene, rs17465637 in MIA3 gene, rs7025486 in DAB2IP gene, rs17228212 in SMAD3 gene, rs981887 in MRAS gene and rs1746048 in CXCL12 gene, by TaqMan and KASPar allele discrimination techniques. Serum lipid parameters were measured using commercially available kits. Statistical analyses were done using SPSS version 22.ResultsIndividually, the single SNPs were not associated with CAD (p < 0.05). However, the combined GRS of 6 SNPs was significantly higher in cases than controls (4.89 ± 0.11 vs 4.58 ± 0.08, p = 0.024). Among blood lipids, GRS showed significant positive association with serum triglycerides levels (p = 0.022).ConclusionThe GRS was quantitatively associated with CAD risk and showed association with serum triglycerides levels, suggesting that the mechanism of these variants is likely to be in part at least through creating an atherogenic lipid profile in subjects carrying high numbers of risk alleles.Electronic supplementary materialThe online version of this article (10.1186/s12944-018-0736-2) contains supplementary material, which is available to authorized users.

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“…Due to recent explosion of the obesity World Health Organization (WHO) has designated obesity a global epidemic. Obesity is a heterogeneous disorder involving a complex interaction of multitude of including environmental, behavioural and genetic factors, none of which are completely understood [1]. Genetic studies on obesity started as a result of the observation that family clustering occurs in obesity.…”

Section: Introductionmentioning

confidence: 99%

The p. N103K mutation of leptin (LEP) gene and severe early onset obesity in Pakistan

Shabana

Hasnain

2016

Biol Res

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BackgroundObesity is a complex disorder and has been increasing globally at alarming rates including Pakistan. However, there is scarce research on understanding obesity genetics in Pakistan. Leptin is a hormone secreted by adipocytes in response to satiety and correlates with body weight. Any mutations in the LEP gene have an adverse effect on energy regulation pathway and lead to severe, early onset obesity. To date, only eight mutations have been described in the LEP gene of which p. N103K is one.MethodsWe aimed to analyze the prevalence of this mutation in Pakistani subjects. A total of 475 subjects were genotyped by PCR–RFLP analysis and their serum profiling was done.ResultsResults showed that this mutation was present only in one male child with early onset obesity (10 year). He had very low serum leptin levels suggestive of functional impact of the mutation. The prevalence of such mutations is, however, low due to the drastic effects on the energy regulation.ConclusionIn conclusion, LEP gene mutations contribute significantly to the monogenic forms of obesity and are important due to the availability of treatment options. Such mutations may exert their effect by directly affecting energy regulation pathway and are more prominent in the early stages of life only.

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Effect of six type II diabetes susceptibility loci and an FTO variant on obesity in Pakistani subjects

Cited by 25 publications

References 59 publications

Genetical Genomics of Tonic Immobility in the Chicken

Genetical Genomics of Tonic Immobility in the Chicken

GWAS implicated risk variants in different genes contribute additively to increase the risk of coronary artery disease (CAD) in the Pakistani subjects

The p. N103K mutation of leptin (LEP) gene and severe early onset obesity in Pakistan

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