Table 3. PPARβ/δ single nucleotide polymorphisms associated with disease.
| SNPs Reference | HGVS Names | Chr 6 position |
Functional position |
Sequence | Associated manifestations | References |
|---|---|---|---|---|---|---|
| rs1053049 | *1762C>T | 35395618(+) | 3’ UTR | CCCTAT/CGGGCG | ↓ Loss of fat mass and hepatic lipid after Life Intervention Heterozygous minor allele carrier present ↑ mRNA expression of PPARβ/δ, associated with ↑ADIPOR1 expression. |
[Thamer et al., 2008], [Ordelheide et al., 2011] |
| rs6902123 | -102+15494T>C | 35330421(+) | Intron | CCTGGT/CGCTGT | ↑ Insulin Resistance and risk of diabetes; no change in mRNA expression levels. ↑ Risk of diabetes in women ↑ Risk of diabetes in elderly Chinese ↓ Loss of fat mass and hepatic lipid after Life Intervention |
[Andrulionyte et al., 2006], [Cresci, 2008], [Lu et al., 2012], [Thamer et al., 2008] |
| rs2267668 | -101-842G>A | 35377922(+) | Intron | TATCTA/GAGAGT | ↑ aerobic physical fitness and insulin sensitivity ↓ Loss of fat mass after Life Intervention ↑ mRNA expression of PPARβ/δ Not associated with higher longevity |
[Stefan et al., 2007], [Thamer et al., 2008], [Ordelheide et al., 2011], [Santiago et al., 2013] |
| rs2016520 | -87C>T or T+294C | 35378778(-) | 5’UTR Exon 4 Exonic splicing enhancer |
ACAGGA/GTGGTT | ↑ plasma LDL cholesterol ; the rare variant 5’UTR confers higher PPARβ/δ expression ↓ plasma cholesterol level in Alzheimer's disease subject but not in controls ↓ plasma HDL concentrations in woman. ↑ Coronary heart disease ↑ plasma cholesterol ↑ and ↓ body mass index in women and men, respectively. ↓ and ↑ HDL cholesterol in women and men, respectively. ↓ obesity risk in Chinese Han population ↑ fasting insulin levels and ↓insulin sensitivity in Polycystic ovary syndrome ↑ fasting plasma glucose in HGT or diabetic Chinese subject/ impaired insulin sensitivity ↓ stature in both adults and children Associated with elite-level endurance athletes ↑ risk of chronic kidney disease |
[Skogsberg et al., 2003], [Holzapfel et al., 2006], [Aberle et al., 2006; Nikitin et al., 2010], [Gallicchio et al., 2008], [Burch et al., 2010], [Luo et al., 2013], [San-Millan and Escobar-Morreale, 2010], [Hu et al., 2006], [Burch et al., 2009], [Eynon et al., 2009], [Hishida et al., 2013] |
| rs3734254 | *1154C>T | 35395010(+) | 3’UTR | CTGCCT/CCTCCA | ↑ risk of diabetes; no change in mRNA levels No significant association with plasma cholesterol levels in Alzheimer patients |
[Andrulionyte et al., 2006], [Holzapfel et al., 2006] |
| rs9794 | *1939G>A or *1939G>C | 35395795(+) | 3’UTR Exon 9 |
GCCCCA/C/GACCCG | ↓ plasma cholesterol in Alzheimer's disease patients Hypertriglyceridemia in Chinese Han Population ↓ Obesity risk in Chinese Han Population |
[Holzapfel et al., 2006], [Gu et al., 2013], [Luo et al., 2013] |
| rs2267665 | -101-9273A>G | 35369491(+) | Intron | GTGCCG/ACACCT | Significant association with susceptibility to Bipolar disorder using a family-based study | [Zandi et al., 2008] |
| rs9462082 | 131-1863A>G | 35386041(+) | Intron | CAGGCA/GTCCAC | Significant association with susceptibility to Bipolar disorder using a family-based study | [Zandi et al., 2008] |
| rs2076167 | c.489C>T | 35391787(-) | Exon 6 -substitution N [Asn] ⇒ N [Asn] -Coding synonimous |
CCCTCA/GTTTGC | ↑obesity risk | [Saez et al., 2008] |
| rs2076168 | 424+264G>A or 424+264G>T | 35389999(-) | Intron | GAATGA/C/TGTAAA | ↓ PPARβ/δ mRNA expression of rare allele. PPARβ/δ basal level of expression correlates with slow and fast twitch markers expression. | [Nilsson et al., 2007] |
| rs2076169 | 285+421A>G | 35388479(-) | Intron | AGATTT/CTGATG | ↑ insulin sensitivity | [Grarup et al., 2007] |
PPARβ/δ SNPs associated with diseases are listed according to SNPs Reference, Human Genome Variation Society (HGVS) nomenclature, chromosome and functional position. The target sequences are also reported together with the main observations on associated disease phenotype.