TABLE 1.
Lammert and Sauerbruch's 2008 inventory of human cholesterol gallstone (LITH) genesa
| Databases |
Frequency |
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Genes | Gene Symbols | Function | OMIMb,c | Genecardsd | Rare Monogenic | Familial Oligogenic | Common Polygenic | Gene Variants | Mouse Model | Concordant Mouse Lith Loci | Potential Mechanisms |
| ABC transporter B4 | ABCB4 (GBD1) | Hepatocanalicular phosphatidylcholine (lecithin) flippase | 171060 and 600803 | GC07M 086676 | + | Multiple | + | Biliary phospholipid secretion ↓ | |||
| ABC transporter B11 | ABCB11 | Hepatocanalicular bile salt export pump | 603201 | GC02M 169604 | + | Multiple | (+) | Lith1 | Biliary bile salt secretion ↓ | ||
| ABC transporters G5/G8 | ABCG5/G8 (GBD4) | Hepatocanalicular cholesterol transporter | 605459/605460 and 611465 | GC02P 043951/GC02P 043977 | + (Germany Sorbs, Chile, China) | ABCG8 p.D19H (rs1188753) | + | Lith9 | Biliary cholesterol secretion ↑ | ||
| β3 Adrenergic receptor | ARDB3 | 109691 | GC08M 037939 | (+) (Germany) | p.R64W (rs4944) | Gallbladder hypomotility | |||||
| Apolipoprotein A1 | APOA1 | 107680 | GC11M 116211 | (+) (China, India) | −75G>A, RFLP | Biliary cholesterol secretion ↑ secondary to reverse cholesterol transport ↑ | |||||
| Apolipoprotein B | APOB | 107730 | GC02M 021135 | + | (+) (China, Poland) | c.2488C>T, c.4154G>A | + | Biliary cholesterol secretion ↑ secondary to hepatic VLDL synthesis ↓ and intestinal cholesterol absorption ↑ | |||
| Apolipoprotein C1 | APOC1 | 107710 | GC19P 050109 | (+) (India) | RFLP | APOC1 ↑ remnant-like particle cholesterol ↑ | |||||
| Androgen receptor | AR | 313700 | GC0XP 066680 | (+) (Greece) | c.172(CAG)n | ||||||
| Cholecystokinin 1 receptor | CCK1R | 118444 | GC04M 026159 | + | (+) (India) | RFLP | + | Lith13 | Gallbladder and small intestinal hypomotility | ||
| Cholesterol ester transfer protein | CETP | 118470 | GC16P 055553 | (+) (Finland) | RFLP | Gene absent in mice | Hepatic cholesterol uptake ↑ from HDL catabolism ↑ | ||||
| Cytochrome P450 7A1 | CYP7A1 | Cholesterol 7α-hydroxylase (rate-limiting enzyme of bile salt synthesis) | 118470 | GC08M 059565 | + | (+) (China) | Promoter SNP −204A>C | + | Bile salt synthesis ↓ | ||
| Estrogen receptor 2 | ESR2 | Estrogen receptor β | 601663 | GC14M 063621 | (+) (Greece) | c.1092+3607(CA)n | (+) | Cholesterol synthesis ↑ | |||
| Low-density lipoprotein receptor-related protein associated protein 1 | LRPAP1 | 104225 | GC04M 003551 | (+) (India) | Intron 5 insertion/deletion (rs11267919) | + | Lith13 | Hepatic cholesterol uptake ↑ from chylomicron remnants via LRP ↑ | |||
a
Reproduced from Ref. 38 (slightly modified) by permission of the copyright holders (Springer-Verlag/Falk Foundation) and the authors; individual references are cited therein.
b
Abbreviations used: OMIM, Online Mendelian inheritance in man; GBD, gallbladder disease; RFLP, restriction fragment length polymorphism; SNP, single nucleotide polymorphism; LRP, low-density lipoprotein receptor-related protein.