Evidence for sex-specific associations between variation in acid phosphatase locus 1 (ACP1) and insulin sensitivity in Mexican-Americans.
BACKGROUND
Acid phosphatase locus 1 (ACP1) is a low molecular weight tyrosine phosphatase that has been shown to be an important regulator of insulin receptor signaling.


OBJECTIVE
We tested whether variation in ACP1 is associated with type 2 diabetes-related traits in 1035 individuals in 339 Mexican-American families of probands with or without a previous diagnosis of gestational diabetes mellitus (GDM).


METHODS
Study participants were phenotyped by oral glucose tolerance test (for glucose and insulin level) and iv glucose tolerance test (for insulin sensitivity and acute insulin response) and had dual-energy x-ray absorptiometry scans to assess body composition. Six tag single nucleotide polymorphisms (SNPs) were identified from among 15 SNPs genotyped across the ACP1 region. SNPs were tested for association with phenotypes using a likelihood ratio test under a variance components framework.


RESULTS
After Bonferroni correction, none of the SNPs were associated with type 2 diabetes mellitus-related phenotypes. However, we observed a significant sex-specific effect of rs3828329. Among males, rs3828329 was significantly associated with fasting insulin (Bonferroni P = 0.007) and insulin sensitivity (Bonferroni P = 0.019) and marginally associated with 2-h insulin (Bonferroni P = 0.058) and percentage body fat (Bonferroni P = 0.09).


CONCLUSIONS
There were no significant associations in females. We conclude that variation in ACP1 is associated with fasting insulin and insulin sensitivity in a sex-specific manner.
Shu
Yu-Hsiang
YH
Department of Preventive Medicine, Division of Biostatistics, Keck School of Medicine of the University of Southern California, Los Angeles, California 90033, USA.
Hartiala
Jaana
J
Xiang
Anny H
AH
Trigo
Enrique
E
Lawrence
Jean M
JM
Allayee
Hooman
H
Buchanan
Thomas A
TA
Bottini
Nunzio
N
Watanabe
Richard M
RM
D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D016640:Diabetes, Gestational / Q000235:genetics; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D017058:Mexican Americans / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011972:Receptor, Insulin / Q000378:metabolism; D012737:Sex Factors; D015398:Signal Transduction
D011518:Proto-Oncogene Proteins; D011972:Receptor, Insulin; C490429:ACP1 protein, human; D017027:Protein Tyrosine Phosphatases