Редактирование: ACP2 (раздел)

==Publications==

{{medline-entry
|title=Association of levels of fasting glucose and insulin with rare variants at the chromosome 11p11.2-[[MADD]] locus: Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24951664
|abstract=Common variation at the 11p11.2 locus, encompassing [[MADD]], [[ACP2]], [[NR1H3]], [[MYBPC3]], and [[SPI1]], has been associated in genome-wide association studies with fasting glucose and insulin (FI). In the Cohorts for Heart and Aging Research in Genomic Epidemiology Targeted Sequencing Study, we sequenced 5 gene regions at 11p11.2 to identify rare, potentially functional variants influencing fasting glucose or FI levels. Sequencing (mean depth, 38×) across 16.1 kb in 3566 individuals without diabetes mellitus identified 653 variants, 79.9% of which were rare (minor allele frequency <1%) and novel. We analyzed rare variants in 5 gene regions with FI or fasting glucose using the sequence kernel association test. At [[NR1H3]], 53 rare variants were jointly associated with FI (P=2.73×10(-3)); of these, 7 were predicted to have regulatory function and showed association with FI (P=1.28×10(-3)). Conditioning on 2 previously associated variants at [[MADD]] (rs7944584, rs10838687) did not attenuate this association, suggesting that there are >2 independent signals at 11p11.2. One predicted regulatory variant, chr11:47227430 (hg18; minor allele frequency=0.00068), contributed 20.6% to the overall sequence kernel association test score at [[NR1H3]], lies in intron 2 of [[NR1H3]], and is a predicted binding site for forkhead box A1 ([[FOXA1]]), a transcription factor associated with insulin regulation. In human HepG2 hepatoma cells, the rare chr11:47227430 A allele disrupted [[FOXA1]] binding and reduced [[FOXA1]]-dependent transcriptional activity. Sequencing at 11p11.2-[[NR1H3]] identified rare variation associated with FI. One variant, chr11:47227430, seems to be functional, with the rare A allele reducing transcription factor [[FOXA1]] binding and [[FOXA1]]-dependent transcriptional activity.
|mesh-terms=* Aged
* Aged, 80 and over
* Aging
* Blood Glucose
* Chromosomes, Human, Pair 11
* Cohort Studies
* Death Domain Receptor Signaling Adaptor Proteins
* Diabetes Mellitus, Type 2
* Fasting
* Female
* Gene Frequency
* Genetic Variation
* Genome-Wide Association Study
* Genomics
* Guanine Nucleotide Exchange Factors
* Heart Diseases
* Humans
* Insulin
* Male
* Middle Aged
* Polymorphism, Single Nucleotide
* Sequence Analysis, DNA
|keywords=* genetic epidemiology
* glucose
* human genetics
* insulin
* molecular genetics
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066205
}}