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Evidence for sex-specific associations between variation in acid phosphatase locus 1 (ACP1) and insulin sensitivity in Mexican-Americans.

ABSTRACT: 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.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).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.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).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.

SUBMITTER: Shu YH

PROVIDER: S-EPMC2758733 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Evidence for sex-specific associations between variation in acid phosphatase locus 1 (ACP1) and insulin sensitivity in Mexican-Americans.

Shu Yu-Hsiang YH 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

The Journal of clinical endocrinology and metabolism 20090721 10

<h4>Context</h4>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.<h4>Objective</h4>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).<h4>Design</h4>Study participants were phenotyped by oral glucose tolerance test ...[more]

PMID: 19622628

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Project description:Insulin resistance and hyperinsulinemia are strong correlates of obesity and type 2 diabetes, but little is known about their genetic determinants. Using data on nondiabetics from Mexican American families and a multipoint linkage approach, we scanned the genome and identified a major locus near marker D6S403 for fasting "true" insulin levels (LOD score 4.1, empirical P<.0001), which do not crossreact with insulin precursors. Insulin resistance, as assessed by the homeostasis model using fasting glucose and specific insulin (FSI) values, was also strongly linked (LOD score 3.5, empirical P<.0001) with this region. Two other regions across the genome were found to be suggestively linked to FSI: a location on chromosome 2q, near marker D2S141, and another location on chromosome 6q, near marker D6S264. Since several insulin-resistance syndrome (IRS)-related phenotypes were mapped independently to the regions on chromosome 6q, we conducted bivariate multipoint linkage analyses to map the correlated IRS phenotypes. These analyses implicated the same chromosomal region near marker D6S403 (6q22-q23) as harboring a major gene with strong pleiotropic effects on obesity and on lipid measures, including leptin concentrations (e.g., LOD(eq) for traits-specific insulin and leptin was 4.7). A positional candidate gene for insulin resistance in this chromosomal region is the plasma cell-membrane glycoprotein PC-1 (6q22-q23). The genetic location on chromosome 6q, near marker D6S264 (6q25.2-q26), was also identified by the bivariate analysis as exerting significant pleiotropic influences on IRS-related phenotypes (e.g., LOD(eq) for traits-specific insulin and leptin was 4.1). This chromosomal region harbors positional candidate genes, such as the insulin-like growth factor 2 receptor (IGF2R, 6q26) and acetyl-CoA acetyltransferase 2 (ACAT2, 6q25.3-q26). In sum, we found substantial evidence for susceptibility loci on chromosome 6q that influence insulin concentrations and other IRS-related phenotypes in Mexican Americans.

Dataset Information

Evidence for sex-specific associations between variation in acid phosphatase locus 1 (ACP1) and insulin sensitivity in Mexican-Americans.

Publications

Evidence for sex-specific associations between variation in acid phosphatase locus 1 (ACP1) and insulin sensitivity in Mexican-Americans.

Similar Datasets

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