A calpain-10 gene polymorphism is associated with reduced muscle mRNA levels and insulin resistance.
Previous linkage studies in Mexican-Americans localized a major susceptibility locus for type 2 diabetes, NIDDM1, to chromosome 2q. This evidence for linkage to type 2 diabetes was recently found to be associated with a common G-->A polymorphism (UCSNP-43) within the CAPN10 gene. The at-risk genotype was homozygous for the UCSNP-43 G allele. In the present study among Pima Indians, the UCSNP-43 G/G genotype was not associated with an increased prevalence of type 2 diabetes. However, Pima Indians with normal glucose tolerance, who have a G/G genotype at UCSNP-43, were found to have decreased rates of postabsorptive and insulin-stimulated glucose turnover that appear to result from decreased rates of glucose oxidation. In addition, G/G homozygotes were found to have reduced CAPN10 mRNA expression in their skeletal muscle. A decreased rate of insulin-mediated glucose turnover, or insulin resistance, is one mechanism by which the polymorphism in CAPN10 may increase susceptibility to type 2 diabetes mellitus in older persons.
Baier
L J
LJ
Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Phoenix, Arizona 85016, USA. lbaier@phx.niddk.nih.gov
Permana
P A
PA
Yang
X
X
Pratley
R E
RE
Hanson
R L
RL
Shen
G Q
GQ
Mott
D
D
Knowler
W C
WC
Cox
N J
NJ
Horikawa
Y
Y
Oda
N
N
Bell
G I
GI
Bogardus
C
C
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001130:Arizona; D001706:Biopsy; D001786:Blood Glucose / Q000378:metabolism; D002154:Calpain / Q000235:genetics*; D002648:Child; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005838:Genotype; D005951:Glucose Tolerance Test; D006801:Humans; D007198:Indians, North American; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000096:biosynthesis; D009132:Muscles / Q000201:enzymology; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000032:analysis; D012737:Sex Factors
D001786:Blood Glucose; D009124:Muscle Proteins; D012333:RNA, Messenger; D002154:Calpain