NEW YORK (Reuters Health) - Polymorphisms in PTPN1, the gene that encodes protein tyrosine phosphatase-1B, are associated with insulin sensitivity and fasting glucose levels, according to a report in the November issue of Diabetes.
“Researchers are beginning to identify genes that measurably contribute to common diseases in the general population,” Dr. Donald W. Bowden from Wake Forest University School of Medicine, Winston-Salem, North Carolina told Reuters Health. “This has great potential for influencing preventive care and treatment choices for physicians and patients.”
Based on previous research suggesting an association between protein tyrosine phosphatase-1B (PTP-1B) and insulin sensitivity in mice, Dr. Bowden and colleagues evaluated the association of the PTPN1 gene and quantitative measures of glucose homeostasis in 811 Hispanic subjects extensively phenotyped for measures of glucose homeostasis in the Insulin Resistance Atherosclerosis Study Family Study.
All 20 single nucleotide polymorphisms (SNPs) from a region just distal to exon 1 through a portion of the 3' untranslated region of PTPN1 were significantly associated with the insulin sensitivity index, the authors report.
Another 22 SNPs from just proximal to PTPN1 exon 1 to an area distal to exon 10 were significantly associated with fasting glucose levels.
“Something that is of interest is that diabetes risk associated with the PTPN1 gene variant lies solely with nucleotide differences in the non-protein coding region of the gene (i.e., the proteins that are made by each genetic form of the PTPN1 gene are identical),” Dr. Bowden said. “We presume that the difference in risk is due to levels or stability of the PTPN1 message being different in people with different variants, which ultimately lead to differences in protein levels.”
None of the SNPs, however, were associated with measures of beta-cell function, the report indicates.
Haplotype ACTTCAG0, which is associated with type 2 diabetes risk in Caucasians, was significantly associated with greater insulin resistance and higher fasting glucose, the researchers note. In contrast, haplotype GTCCTGT0, which is associated with protection from type 2 diabetes in Caucasians, was significantly associated with greater insulin sensitivity and lower fasting glucose in these subjects.
“This comprehensive genetic analysis of PTPN1 reveals significant association with metabolic traits consistent with the proposed in vivo role for the PTP-1B protein [in insulin sensitivity],” the authors conclude.
“It is premature to think that the haplotypes will be immediately useful in identifying high-risk individuals,” Dr. Bowden cautioned. “It would be necessary to perform a controlled clinical trial to see if they have predictive value. In addition to PTPN1, other diabetogenic forms of genes are also likely to contribute to risk for developing diabetes in addition to the lifestyle risk factors such as obesity.”
Source: Diabetes 2004;53:3013-3019. [ Google search on this article ]
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