No genetic association of the human prolyl endopeptidase gene in the Dutch celiac disease population

Celiac disease (CD) is a complex genetic disorder of the small intestine. The DQ2/DQ8 human leucocyte antigen (HLA) genes explain ∼40% of the genetic component of the disease, but the remaining non-HLA genes have not yet been identified. The key environmental factor known to be involved in the disease is gluten, a major protein present in wheat, barley, and rye. Integrating microarray data and linkage data from chromosome 6q21–22 revealed the prolyl endopeptidase ( PREP) gene as a potential CD candidate in the Dutch population. Interestingly, this gene encodes for the only enzyme that is able to cleave the proline-rich gluten peptides. To investigate the role of the human PREP gene as a primary genetic factor in CD, we conducted gene expression, sequence analysis, and genetic association studies of the PREP gene and determined PREP enzyme activity in biopsies from CD patients and controls. Sequence analysis of the coding region of the PREP gene revealed two novel polymorphisms. Genetic association studies using two novel polymorphisms and three known PREP variants excluded a genetic association between PREP and CD. Determination of PREP activity revealed weak but significant differences between treated and untreated CD biopsies ( P < 0.05). Our results from the association study indicate that PREP is not a causative gene for CD in the Dutch population. These are further supported by the activity determinations in which we observed no differences in PREP activity between CD patients and controls.

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Statistical methods for multi-marker testing in genetic association studies

10.37099/mtu.dc.etd-restricted/82 ◽

2012 ◽

Author(s):

Yilin Dai

Keyword(s):

Genetic Association ◽

Statistical Methods ◽

Association Studies ◽

Genetic Association Studies

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Fine scale human genetic structure in three regions of Cameroon reveals episodic diversifying selection

Scientific Reports ◽

10.1038/s41598-020-79124-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kevin K. Esoh ◽

Tobias O. Apinjoh ◽

Steven G. Nyanjom ◽

Ambroise Wonkam ◽

Emile R. Chimusa ◽

...

Keyword(s):

Genetic Structure ◽

Ethnic Groups ◽

Genetic Association ◽

Association Studies ◽

Genetic Association Studies ◽

Genomic Region ◽

Sub Saharan Africa ◽

Genome Wide Association Studies ◽

Fine Scale ◽

Sub Saharan

AbstractInferences from genetic association studies rely largely on the definition and description of the underlying populations that highlight their genetic similarities and differences. The clustering of human populations into subgroups (population structure) can significantly confound disease associations. This study investigated the fine-scale genetic structure within Cameroon that may underlie disparities observed with Cameroonian ethnicities in malaria genome-wide association studies in sub-Saharan Africa. Genotype data of 1073 individuals from three regions and three ethnic groups in Cameroon were analyzed using measures of genetic proximity to ascertain fine-scale genetic structure. Model-based clustering revealed distinct ancestral proportions among the Bantu, Semi-Bantu and Foulbe ethnic groups, while haplotype-based coancestry estimation revealed possible longstanding and ongoing sympatric differentiation among individuals of the Foulbe ethnic group, and their Bantu and Semi-Bantu counterparts. A genome scan found strong selection signatures in the HLA gene region, confirming longstanding knowledge of natural selection on this genomic region in African populations following immense disease pressure. Signatures of selection were also observed in the HBB gene cluster, a genomic region known to be under strong balancing selection in sub-Saharan Africa due to its co-evolution with malaria. This study further supports the role of evolution in shaping genomes of Cameroonian populations and reveals fine-scale hierarchical structure among and within Cameroonian ethnicities that may impact genetic association studies in the country.

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Patterns of linkage disequilibrium atPARK16may explain variances in genetic association studies

Movement Disorders ◽

10.1002/mds.26176 ◽

2015 ◽

Vol 30 (10) ◽

pp. 1335-1342 ◽

Cited By ~ 6

Author(s):

Huihua Li ◽

Yik-Ying Teo ◽

Eng-King Tan

Keyword(s):

Linkage Disequilibrium ◽

Genetic Association ◽

Association Studies ◽

Genetic Association Studies

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Evaluation of genome-wide power of genetic association studies based on empirical data from the HapMap project

Human Molecular Genetics ◽

10.1093/hmg/ddm205 ◽

2007 ◽

Vol 16 (20) ◽

pp. 2494-2505 ◽

Cited By ~ 23

Author(s):

Yasuhito Nannya ◽

Kenjiro Taura ◽

Mineo Kurokawa ◽

Shigeru Chiba ◽

Seishi Ogawa

Keyword(s):

Genetic Association ◽

Empirical Data ◽

Association Studies ◽

Genetic Association Studies ◽

Hapmap Project ◽

Genome Wide

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Clinical, biochemical and genetic risk factors for 30-day and 5-year mortality in 518 adult patients subjected to cardiopulmonary bypass during cardiac surgery - the INFLACOR study.

Acta Biochimica Polonica ◽

10.18388/abp.2017_2361 ◽

2018 ◽

Vol 65 (2) ◽

pp. 241-250 ◽

Cited By ~ 3

Author(s):

Maciej Michał Kowalik ◽

Romuald Lango ◽

Piotr Siondalski ◽

Magdalena Chmara ◽

Maciej Brzeziński ◽

...

Keyword(s):

Risk Factors ◽

Cardiac Surgery ◽

Cardiopulmonary Bypass ◽

Genetic Association ◽

Biochemical Parameters ◽

Cox Regression ◽

Association Studies ◽

Nyha Class ◽

Genetic Association Studies ◽

Chronic Obstructive

There is increasing evidence that genetic variability influence patients’ early morbidity after cardiac surgery performed using cardiopulmonary bypass (CPB). The use of mortality as an outcome measure in cardiac surgical genetic association studies is rare. We publish the 30-day and 5-year survival analyses with focus on pre-, intra-, postoperative variables, biochemical parameters, and genetic variants in the INFLACOR (INFlAmmation in Cardiac OpeRations) cohort.In a series of prospectively recruited 518 adult Polish Caucasians who underwent cardiac surgery in which CPB was used, the clinical data, biochemical parameters, IL-6, soluble ICAM-1, TNFa, soluble E-selectin, and 10 single nucleotide polymorphisms were evaluated for their associations with 30-day and 5-year mortality.The 30-day mortality was associated with: pre-operative prothrombin international normalized ratio, intra-operative blood lactate, postoperative serum creatine phosphokinase, and acute kidney injury requiring renal replacement therapy (AKI-RRT) in logistic regression. Factors that determined the 5-year survival included: pre-operative NYHA class, history of peripheral artery disease and severe chronic obstructive pulmonary disease, intra-operative blood transfusion; and postoperative peripheral hypothermia, myocardial infarction, infection, and AKI-RRT in Cox regression. The serum levels of IL-6 and ICAM-1 measured three hours after operation were associated with 30-day and 5-year mortality, respectively. The ICAM1 rs5498 was associated with 30-day and 5-year survival with borderline significance.Different risk factors determined the early (30-day) and late (5-year) survival after adult cardiac surgery in which cardiopulmonary bypass was used. Future genetic association studies in cardiac surgical patients should adjust for the identified chronic and acute postoperative risk factors.

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