Genetic predisposition to diabetes high in Indians
Published in The Hindu on May 4, 2006
Blame it on your genes. After all, you are what you are because of your genes. While the role of genes in determining the colour of one’s eyes or appearance has been accepted, their role in determining behavioural characteristics is still debated. Genes have been found to determine the susceptibility to particular diseases too. It could be a disease linked to a single gene or to a large number of genes. The role of many genes playing a pivotal role in determining the predisposition to diabetes is becoming all the more clear.
Insulin resistance
The genetic cause that predisposes a person to insulin resistance – preventing insulin from helping the cells to take up glucose present in the blood and convert it to energy – has been already shown in a paper published last year in the journal Diabetes. Dr. Mohan and his team from the Dr. Mohan’s Diabetes Specialities Centre, Chennai, and Nicola Abate and Manish Chandalia from the University of Texas Southwestern Medical Center, Dallas, U.S., found that a particular variation in the gene ENPP1 tends to increase the susceptibility to Type II diabetes in both Caucasians and South Asians.
ENPP1 encodes a protein that is responsible for blocking the action of insulin leading to insulin resistance. The genetic variation was found to further increase the action of the protein leading to greater insulin resistance. Now a paper published online a few days ago in the journal Diabetes Care has gone one step further.
“Indians are known to have more insulin resistance and [hence] are more prone to becoming diabetic even in the absence of obesity as defined by BMI,” said Dr. V. Mohan “In order to understand the mechanism of insulin resistance [even in the absence of obesity], we studied several genes involved in the insulin action pathway.” While several genes have been postulated to produce defective insulin signalling leading to insulin resistance, the Pro12Ala of PPAR-gamma2 (Peroxisome Proliferator-Activated Receptor – gamma2) gene has been found to provide protection from Type II diabetes.Polymorphism arises when there is a sequence variation in the DNA (the four nucleotides – Adenine, Cytosine, Guanine and Thymidine) and should be seen in at least 1 in 100.
Reduced incidence
The presence of polymorphism P12A in PPAR-gamma gene has been known to produce improved insulin sensitivity and hence reduced incidence of diabetes. Earlier studies have shown the protective effect offered by this polymorphism to be around 20 per cent. “If this theory is indeed true, then we should see this [polymorphism] more in those who are not diabetic,” Dr. Mohan stated. “And fewer people who are already diabetic should have this polymorphism.” The polymorphism does what it should do in Caucasians as brought out in the study done by Dr. Radha Venkatesan and Dr. Mohan from the Dr. Mohan’s Diabetes Specialty Centre and the Dallas team. That was not the case with Indians though.
Unexpected findings
The frequency of occurrence of this polymorphism in Indians was the same in those who were diabetic as well as those who were not. In the case of Caucasians, the frequency was greater in non-diabetics compared with diabetics. Further, considering the protective effect of this polymorphism, the number of people in India having this polymorphism should be lower, as India has the largest number of diabetics. The study found that South Asians (Indians) defied this as well. The frequency of occurrence of this polymorphism in South Asians and Caucasians was found to be nearly the same – about 11 and 10 per cent respectively.”Our study showed the polymorphism offered greater protection to Caucasians but not to Indians,” Dr. Mohan underlined.
Several other studies published in the past have shown the role of genetic factors that greatly predispose Indians to diabetes. The prevalence of the disease even at a younger age was brought out in a study published in Diabetologia in 2003. Dr. Mohan and his team showed in a paper published last year in the journal Diabetes Care that a polymorphism in HNF -1alpha gene reduced the onset age of the disease. The age at diagnosis of Type II diabetes in those with a particular genotype (valine-valine) was nearly 11 years earlier than those who had another genotype (alanine-alanine).
While its has been documented that the prevalence of the disease in Indians was higher even when their BMI (body mass index) was lower than Caucasians, another study showed that the prevalence of visceral fat in the abdominal region in Indians was higher compared with Caucasians even when their waist-hip ratios were matched. Visceral fat has been shown to make people susceptible to diabetes.
