Genetic risk factors and the anti-atherosclerotic effect of pioglitazone on carotid atherosclerosis of subjects with type 2 diabetes--a retrospective study.
OBJECTIVE
Pioglitazone, an agonist of peroxisome proliferator-activated receptor gamma, showed various anti-atherosclerotic effects on type 2 diabetic patients. This retrospective study was done to ascertain which risk factor(s) associate with anti-atherosclerotic effects of pioglitazone.


METHODS
We enrolled 160 diabetic patients treated through diet only and 62 treated with pioglitazone and annually evaluated carotid maximum (MaxIMT) and averaged intima-media thickness (AveIMT) for 2 years. We analyzed the relation of 99 single-nucleotide polymorphisms (SNP) as well as conventional risk factors with the progression or regression of carotid atherosclerosis.


RESULTS
The D allele of the angiotensin-converting enzyme (ACE) gene and 677 allele of the methylene-tetrahydrofolate reductase (MTHFR) gene showed a significant association with increases in MaxIMT among the diabetic subjects treated through diet only. The pioglitazone-treated carriers of the D allele showed an attenuation of MaxIMT as compared with the diet-treated carriers. The pioglitazone-treated carriers of the 677T allele carriers showed a significant attenuation of MaxIMT compared with the diet-treated carriers.


CONCLUSIONS
Pioglitazone may exert anti-atherosclerotic effects on type 2 diabetics carrying the ACE gene's D allele and/or MTHFR gene's 677T allele, who showed a progression of carotid atherosclerosis without the drug.
Naka Kinen Clinics, Japan.
Miyoko
M
Saitou
Takeshi
T
Osonoi
Ryuzo
R
Kawamori
Naoto
N
Katakami
Hideaki
H
Kaneto
Munehide
M
Matsuhisa
Yoshimistu
Y
Yamasaki
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002340:Carotid Artery Diseases / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D000077205:Pioglitazone; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D045162:Thiazolidinediones / Q000627:therapeutic use*
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D007703:Peptidyl-Dipeptidase A; D000077205:Pioglitazone