NucleaRDB: Extraction of mutation data from the literature

2005, NucleaRDB.

This data was extracted from Medline abstracts and full texts (when available) in an automated manner.

The table below describes the selected point mutation and provides links to other documents. The sentence(s) where the point mutation P12A was found are listed after the table.

The mutated residues are also indicated in the family sequence alignments and hyperlinked to the corresponding mutation pages.

Point mutation P12A in PPAT_HUMAN

Point mutation:	P12A
Cited point mutation:	Pro12Ala
Domain:	N-term
General numbering (NucleaRDB):	-
Protein:	PPAT_HUMAN (PPARG,NR1C)	Swiss-Prot Cross-reference table Family page
Protein isoforms	2
Other point mutations / same protein / same position	Point mutations at position 12 in PPAT_HUMAN
Other point mutations / same protein	List of mutations in PPAT_HUMAN
Family alignments	1C3 PPAR gamma 1C Peroxisome proliferator activated (PPAR) 1 Thyroid hormone like (TR,RAR,ROR,PPAR,VDR
Other point mutations / same position
Reference:	Genetic variation in fatty acid-binding protein-4 and peroxisome proliferator-activated receptor gamma interactively influence insulin sensitivity and body composition in males. Damcott CM, Moffett SP, Feingold E, Barmada MM, Marshall JA, Hamman RF, Ferrell RE Metabolism 2004 Mar;53(3):303-9.	Medline
Other point mutations / same article	List
Text source	HTML full text
Validation status	Not yet checked

Relevant sentences:

Pro12Ala

In this study , we tested the hypothesis that the polymorphisms , FABP4-376 and PPAR(image) Pro12Ala , interactively influence insulin sensitivity and body composition in nondiabetic , Hispanic and non-Hispanic white males (n = 314) participating in the San Luis Valley Diabetes Study (SLVDS)
While the PPAR(image) Pro12Ala site was the only statistically significant predictor of fat mass in the 2-way model (P = .012) , the FABP4 and PPAR(image) main effect terms individually became stronger when considered in one model compared with the analysis of each polymorphism separately
17 Association studies of the Pro12Ala site involving BMI have shown variable results
18 -23 However , in a large study of Scandinavian individuals , the Pro12Ala variant was the only polymorphism out of 16 common single nucleotide polymorphisms (SNPs) in candidate genes that were previously reported to influence diabetes risk to show a reproducible association with reduced diabetes risk
The previously reported Pro12Ala polymorphism in the PPAR(image) gene (C to G transversion) was detected using an engineered BstUI restriction enzyme site
Two-way ANCOVA was used to explore the multilocus effects and interactions between the FABP4 -376 and PPAR(image) Pro12Ala sites on each outcome variable
The PPAR(image) Pro12Ala variant , originally reported by Yen et al , 15 was also genotyped
Table 1(image) shows the genotype counts and allele frequencies for the FABP4 -376 and PPAR(image) Pro12Ala polymorphic sites
Two-Way ANCOVA for HOMA-IR ------------------------------------------------------------------------ > Model(image)-CoefficientsP ValueR2 (P value)All malesConstant27.2<.001.065 (.004)FABP4 -376 (AA)-8.0.158PPAR(image) Pro12Ala (CC)-8.3.123FABP4 (AA) * PPAR(image) (CC)10.2.014Ethnicity (Hispanic)3.6.011Age (yr)-0.06.299Physical activity (kcal / kg / h)-0.02.065Smoking status (ever smoked)2.3.114Non-Hispanic white malesConstant20.3.005.053 (.114)FABP4 -376 (AA)-6.4.182PPAR(image) Pro12Ala (CC)-4.1.855FABP4 (AA) * PPAR(image) (CC)7.4.076Age (yr)0.06.432Physical activity (kcal / kg / h)-0.02.073Smoking status (ever smoked)2.5.112Hispanic malesConstant50.5<.001.088 (.094)FABP4 -376 (AA)-14.6.401PPAR(image) Pro12Ala (CC)-20.2.053FABP4 (AA) * PPAR(image) (CC)20.9.034Age (yr)-0.2.090Physical activity (kcal / kg / h)-0.02.311Smoking status (ever smoked)3.7.227 ------------------------------------------------------------------------ > In the model for the entire male cohort , the interaction between the FABP4 and PPAR sites was a statistically significant predictor of HOMA-IR (P = .014)
Bar chart of adjusted means for HOMA-IR in the FABP4 -376 / PPAR(image) Pro12Ala genotype groups
Two-Way ANCOVA for Lean Mass (g) ------------------------------------------------------------------------ > Model(image)-CoefficientsP ValueR2 (P value)All males (n = 297)Constant76 , 973<.001.330 (<.001)FABP4 -376 (AA)-4 , 927.140PPAR(image) Pro12Ala (CC)-3 , 778.210FABP4 (AA) * PPAR(image) (CC)4 , 930.019Ethnicity (Hispanic)-6 , 578<.001Age (yr)-204<.001Physical activity (kcal / kg / h)6.191Smoking status (ever smoked)890.234Non-Hispanic white males (n = 180)Constant67 , 257<.001.120 (.001)FABP4 -376 (AA)-5 , 281.084PPAR(image) Pro12Ala (CC)-3 , 985.464FABP4 (AA) * PPAR(image) (CC)6 , 060.020Age (yr)-146.002Physical activity (kcal / kg / h)3.615Smoking status (ever smoked)2 , 140.032Hispanic males (n = 117)Constant65 , 189<.001.295 (<.001)FABP4 -376 (AA)64.641PPAR(image) Pro12Ala (CC)-848.993FABP4 (AA) * PPAR(image) (CC)1 , 664.659Age (yr)-261<.001Physical activity (kcal / kg / h)5.492Smoking status (ever smoked)-689.568 ------------------------------------------------------------------------ > For all males , the interaction between the FABP4 and Pro12Ala sites was a statistically significant predictor of lean mass ( P = .019)
Bar chart of adjusted means for lean mass in the FABP4 -376 / PPAR(image) Pro12Ala genotype groups
Two-Way ANCOVA for Fat Mass (g) ------------------------------------------------------------------------ > Model(image)-CoefficientsP ValueR2 (P value)All males (n = 297)Constant35 , 071<.001.065 (.006)FABP4 -376 (AA)-4 , 485.070PPAR(image) Pro12Ala (CC)-5 , 390.012FABP4 (AA) * PPAR(image) (CC)4 , 205.106Ethnicity (Hispanic)-2 , 650.004Age (yr)-42.283Physical activity (kcal / kg / h)-3.625Smoking status (ever smoked)1 , 146.217Non-Hispanic white males (n = 180)Constant28 , 871<.001.070 (.047)FABP4 -376 (AA)-6 , 458.014PPAR(image) Pro12Ala (CC)-5 , 329.086FABP4 (AA) * PPAR(image) (CC)5 , 324.085Age (yr)31.561Physical activity (kcal / kg / h)-7.360Smoking status (ever smoked)2 , 349.047Hispanic males (n = 117)Constant31 , 334<.001.068 (.250)FABP4 -376 (AA)1 , 436.462PPAR(image) Pro12Ala (CC)-2 , 694.384FABP4 (AA) * PPAR(image) (CC)902.858Age (yr)-125.038Physical activity (kcal / kg / h)-4.695Smoking status (ever smoked)-131.935 ------------------------------------------------------------------------ > The model for the entire male cohort included the Pro12Ala site ( P = .012) as a statistically significant predictor of fat mass
Bar chart of adjusted means for fat mass in the FABP4 -376 / PPAR(image) Pro12Ala genotype groups
In the entire male cohort , we found that individually the FABP4 -376 and the PPAR(image) Pro12Ala variants were not statistically significantly associated with measures of insulin sensitivity and body composition ; however , statistically significant effects were observed when both sites were considered in one model
In particular , carriers of the less common alleles at FABP4 -376 and Pro12Ala showed greater HOMA-IR indices , lean mass , and fat mass
Although the model for fat mass did not show similar evidence of an interactive effect , the Pro12Ala variant was a statistically significant predictor of fat mass when considered in 2-way ANCOVA with FABP4
In previous studies examining the functional effects of the PPAR(image) Pro12Ala site in vitro , the alanine allele has been shown to reduce transcriptional activity , resulting in lower levels of lipolysis and adipogenesis
40 , 41 In this study , individuals with the less common alleles at both the FABP4 -376 and PPAR(image) Pro12Ala show higher HOMA-IR indices (see Fig 1(image) ) , which would be consistent with impaired insulin sensitivity in peripheral tissues through this mechanism
These findings suggest that it is important to consider other genes in the lipid metabolism pathways when evaluating the effects of the PPAR(image) Pro12Ala polymorphism
While we cannot make a definitive conclusion about the interactive effects on fat mass , PPAR(image) Pro12Ala was found to be a significant predictor of fat mass only when considered in a model with the FABP4 variant
J Biol Chem 1997 ; 272:25252-25259.MEDLINE > 15. Yen CJ , Beamer BA , Negri C , et al. Molecular scanning of the human peroxisome proliferator activated receptor gamma (hPPAR gamma) gene in diabetic Caucasians: Identification of a Pro12Ala PPAR gamma 2 missense mutation
Biochem Biophys Res Com mun 2000 ; 268:178-182.MEDLINE > 17. Stumvoll M , Wahl HG , Loblein K , et al. Pro12Ala polymorphism in the peroxisome proliferator-activated receptor- gamma2 gene is associated with increased antilipolytic insulin sensitivity
Diabetes 2001 ; 50:876-881.MEDLINE > 18. Beamer BA , Yen CJ , Andersen RE , et al. Association of the Pro12Ala variant in the peroxisome proliferator-activated receptor- gamma2 gene with obesity in two Caucasian populations
Diabetes 1998 ; 47:1806-1808.MEDLINE > 19. Cole SA , Mitchell BD , Hsueh WC , et al. The Pro12Ala variant of peroxisome proliferator-activated receptor- gamma2 (PPAR- gamma2) is associated with measures of obesity in Mexican Americans
Int J Obes Relat Metab Disord 2000 ; 24:522-524.MEDLINE > 20. Meirhaeghe A , Fajas L , Helbecque N , et al. Impact of the peroxisome proliferator activated receptor gamma2 Pro12Ala polymorphism on adiposity , lipids and non-insulin-dependent diabetes mellitus
Int J Obes Relat Metab Disord 2000 ; 24:195-199.MEDLINE > 21. Deeb SS , Fajas L , Nemoto M , et al. A Pro12Ala substitution in PPAR gamma2 associated with decreased receptor activity , lower body mass index and improved insulin sensitivity
Nat Genet 1998 ; 20:284-287.MEDLINE > 22. Ek J , Urhammer SA , Sorensen TI , et al. Homozygosity of the Pro12Ala variant of the peroxisome proliferation-activated receptor- gamma2 (PPAR- gamma2): Divergent modulating effects on body mass index in obese and lean Caucasian men
Diabetologia 1999 ; 42:892-895.MEDLINE > 23. Mori Y , Kim-Motoyama H , Katakura T , et al. Effect of the Pro12Ala variant of the human peroxisome proliferator-activated receptor gamma 2 gene on adiposity , fat distribution , and insulin sensitivity in Japanese men
Biochem Biophys Res Com mun 1998 ; 251:195-198.MEDLINE > 24. Altshuler D , Hirschhorn JN , Klannemark M , et al. The common PPAR gamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes
Diabetes 2000 ; 49:904-911.MEDLINE > 43. Lei HH , Chen MH , Yang WS , et al. Peroxisome proliferator-activated receptor gamma 2 Pro12Ala gene variant is strongly associated with larger body mass in the Taiwanese
Metabolism 2000 ; 49:1267-1270.MEDLINE > 44. Hara K , Okada T , Tobe K , et al. The Pro12Ala polymorphism in PPAR gamma2 may confer resistance to type 2 diabetes

P12A

Diabetes 2001 ; 50:886-890.MEDLINE > 46. Hegele RA , Cao H , Harris SB , et al. Peroxisome proliferator-activated receptor- gamma2 P12A and type 2 diabetes in Canadian Oji-Cree

F.Horn (nucleardbcmbi.kun.nl), 21-Apr-2005