Table 1.
Lipin gene mutations and polymorphisms associated with human disease
|
LPIN1 mutations | |||
|---|---|---|---|
| Phenotype | Genetic change/locus | Details about change/locus | Reference |
| Recurrent acute myoglobinuria | Homozygous 643 G>T (E215X) | Premature stop codon | 62 |
| Homozygous 1162 C>T (R388X) | Premature stop codon | ||
| 2398 C>T (R800X)/genomic deletion of exons 18 and 19 | Premature stop codon/deletion | ||
| Homozygous 297+2 T>C | Activates cryptic splice site in exon 1; last 106 bp of exon 1 are deleted | ||
| 1259+2 T>C/genomic deletion of exons 18 and 19 (heterozygous) | Skips exon 8/deletion | ||
| Statin-induced myopathy | 2306 A>G (Glu769Gly) | Mutation of a highly conserved amino acid; impaired PAP activity in yeast | 62 |
| LPIN1 polymorphisms | |||
| Body mass index | |||
| rs13412852 | Noncoding SNP | 18 | |
| (Association found in lean men only) | rs893346 A/G, rs2577262 A/G, rs2716610 C/T | Noncoding SNPs | 53 |
| (Association found in obese men only) | rs11693809 C/T, rs10192566 C/G, rs2278513 C/T, rs2577262 A/G | Noncoding SNPs | 53 |
| Haplogroup encompassing SNPs rs33997857, rs6744682, rs6708316 | One exonic SNP leads to a codon change (V494M) and two are intronic; one risk and two protective haplotypes identified | 58 | |
| Insulin levels | |||
| Higher serum insulin | rs11693809 T allele (SNP) | Noncoding SNP | 53 |
| Higher fasting insulin (generation specific) | rs2716609 C allele (SNP) | Noncoding SNP | 36 |
| Waist circumference | |||
| (Generation specific) | rs2716609 C allele (SNP) | Noncoding SNP | 36 |
| Haplogroup encompassing SNPs rs33997857, rs6744682, rs6708316 | One exonic SNP leads to a codon change (V494M) and two are intronic; one risk and two protective haplotypes identified | 58 | |
| Blood pressure | |||
| Lower mean systolic blood pressure (in men only) | rs10495584 G allele (SNP) | Not predicted to be pathogenic, but in high LD with functional SNP rs11524, in which the major allele forms an exonic splicing silencer sequence | 45 |
| Hypertension | D2S0949i (microsatellite) | LPIN1 is the nearest gene to this significantly associated microsatellite | 61 |
| Lower blood pressure | Haplogroup encompassing SNPs rs33997857, rs6744682, rs6708316 | One exonic SNP leads to a codon change (V494M) and two are intronic; one risk and two protective haplotypes identified | 58 |
| Other metabolic phenotypes | |||
| Higher resting metabolic rate (generation specific) | rs2577262 G allele (SNP) | Noncoding SNP | 36 |
| rs2577256 C allele (SNP) | Noncoding SNP | ||
| Metabolic syndrome factor score and A1C levels | Haplogroup encompassing SNPs rs33997857, rs6744682, rs6708316 | One exonic SNP leads to a codon change (V494M) and two are intronic; one risk and two protective haplotypes identified | 58 |
| Type 2 diabetes | Haplotype ATCCG | Haplotype is rare among the Chinese population studied | 10 |
| Improved response to rosiglitazone treatment in type 2 diabetic patients | rs10192566 G allele (SNP) | Noncoding SNP | 29 |
| Elevated hepatic lipase activity (in women only) | rs10192566 G allele (SNP) | Noncoding SNP | 53 |
| LPIN2 mutations | |||
| Majeed syndrome | Homozygous 2201C>T (S734L) | Mutates an amino acid conserved not only across lipins in other species but also in all | 19 |
| HAD family proteins | |||
| Homozygous 540–541delAT | Frameshift mutation; premature stop codon | 19 | |
| Homozygous 2327+1G>C | Mutation of splice site causes an R776S change and a premature stop codon | 1 | |
| Psoriasis | 991G>T (A331S) | All coding changes | 41 |
| 1043C>T (P348L) | |||
| 1159A>G (K387E) | |||
| 1510C>T (L504F) | |||
| 1801G>A (E601K) | |||
| LPIN2 polymorphisms | |||
| Type 2 diabetes and fat distribution | rs3745012 C allele (SNP) | Located within the LPIN2 3′ UTR | 2 |
Abbreviations: HAD, haloacid dehalogenase; LD, linkage disequilibrium; SNP, single nucleotide polymorphism; UTR, untranslated region.