Endogamy may up infertility risk in Indian men

A team of researchers have identified that deletions of the Y chromosomes, responsible for production of sperms, can cause infertility in Indian men.

The study, illustrates how the ethnicity, endogamy and long-time geographical isolation of Indian populations might have played a major role in the high frequencies of deletion events.

According to the researchers, deletions in the AZoospermia Factor (AZF) regions on the human Y chromosome are reported as one of the most common causes of severe testiculopathy and spermatogenic defects leading to male infertility.

For the study, the researchers screened blood samples of 973 infertile men, consisting of 771 azoospermia (complete absence of sperm), 105 oligozoospermia (low sperm count) and 97 oligoteratozoospermia (low sperm count with abnormal shape and size) patients.

The deletion screening was carried out using AZF-specific markers.

The experiments were carried in accordance with the relevant guidelines and regulations approved for research on human samples.

The study revealed deletion events in a total of 29.4 per cent of infertile Indian men. Of these, non-allelic homologous recombination events accounted for 25.8 per cent.

Indian populations are unique in their origin and have been practicing endogamy for the last two thousand years, and therefore it is important to add a study of the frequencies of AZF deletions on the Y chromosome and their association with fertility in Indian idiopathic infertile men to similar studies from other parts of the world, the researchers said.

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Y chromosome loss puts men at higher cancer risk: Study

Loss of Y chromosome, says a study, could explain shorter life expectancy and higher cancer risk for men.

Researchers at Uppsala University in Sweden have shown a correlation between a loss of the Y chromosome in blood cells and both a shorter life span and higher mortality from cancer in other organs.

"Men who had lost the Y chromosome in a large proportion of their blood cells had a lower survival, irrespective of cause of death. We could also detect a correlation between loss of the Y chromosome and risk of cancer mortality," explained Lars Forsberg.

To reach this conclusion, researchers analysed the DNA in blood samples from a group of more than 1,600 elderly men.

They found that the most common genetic alteration was a loss of the Y chromosome in a proportion of the white blood cells.

The group of men was studied for several years and the researchers could detect a correlation between the loss of the Y chromosome and shorter survival.

The results indicate that the Y chromosome has a role in tumour suppression and they might explain why men get cancer more often than women.

"We believe that analyses of the Y chromosome could in the future become a useful general marker to predict the risk for men to develop cancer", added Jan Dumanski, a professor at Uppsala University.

The study was published in the journal Nature Genetics. 

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Not just sex determination, Y chromosome also influences lifespan in men, study reveals

Till now, the all-important Y chromosome — only present in men, and the genes contained on the Y chromosome have mostly been associated with sex determination and sperm production. But scientists have for the first time found that the Y chromosome also influences lifespan in men. 

 It is well known that men have an overall shorter life expectancy compared to women. A study, led by Uppsala University researchers, shows a correlation between a loss of the Y chromosome in blood cells and both a shorter lifespan and higher mortality from cancer in other organs. 

 Men have a shorter average life span than women and both the incidence and mortality in cancer is higher in men than in women. 

 However, the mechanisms and possible risk factors behind this sex-disparity are largely unknown.

 Alterations in DNA of normal cells accumulate throughout our lives and have been linked to diseases such as cancer and diabetes. 

 In a study recently, an international team of researchers have analyzed the DNA in blood samples from a group of more than 1,600 elderly men. 

 They found that the most common genetic alteration was a loss of the Y chromosome in a proportion of the white blood cells. 

 The group of men was studied for many years and the researchers could detect a correlation between the loss of the Y chromosome and shorter survival. 

 "Men who had lost the Y chromosome in a large proportion of their blood cells had a lower survival, irrespective of cause of death. We could also detect a correlation between loss of the Y chromosome and risk of cancer mortality," says Lars Forsberg from Uppsala University. 

 "You have probably heard before that the Y chromosome is small, insignificant and contains very little genetic information. This is not true. Our results indicate that the Y chromosome has a role in tumour suppression and they might explain why men get cancer more often than women. We believe that analyses of the Y chromosome could in the future become a useful general marker to predict the risk for men to develop cancer," says Jan Dumanski, professor at the department of immunology at Uppsala. 

 An average Indian lived 4.6 years longer in 2008 compared to a decade earlier. An average Indian woman lived three years more than her male counterpart in 2008. 

 While the life expectancy at birth for women was 67.7 years, for men it stood at 64.6 years. This was an increase of 2.5 years and 1.8 years, respectively, when compared to the life expectancy (LE) in 2002. According to India's latest life expectancy data, an urban female lived 4.9 years longer than a rural female and 7.9 years longer than a rural male. 

 A woman living in rural Kerala had the highest life expectancy at birth across all categories at 77.2 years.

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Role of Y chromosome in inherited coronary artery disease

Men develop coronary artery disease (CAD) approximately ten years earlier than women.

A study shows that the Y chromosome plays a role. But not every male shares the same risk of developing coronary artery disease, though. Only those belonging to one of the 13 ancient lineages (haplogroup I) were found to be carriers of coronary artery disease risk.

Haplogroup I is associated with increased risk of coronary artery disease. Carriers of haplogroup I are at 50 per cent increased risk of CAD compared with men having different variants. The study also revealed that the increased risk is not mediated by traditional cardiovascular risk factors such as high systolic blood pressure and low HDL cholesterol.

No role

Also, the association between haplogroup I and increased risk of CAD was independent of age and other socioeconomic and lifestyle risk factors such as body-mass index, diabetes, smoking, alcohol consumption, and socioeconomic status.

Predictive value

But the authors caution that the haplogroup I on its own is “unlikely to offer sufficiently high positive predictive value of coronary artery disease.” But they also state in the same breath that the “relative estimates of coronary artery disease risk in carriers of haplogroup I are not trivial” from the genetic association analysis point of view.

Most importantly, the study found that men with haplogroup I showed downregulation (where the cells are made less sensitive to a hormone or another agent) of adaptive immunity that provides much more sophisticated immune response. Previous studies have shown that dysfunction of immune response is a “well established contributor to atherosclerosis and coronary artery disease.”

Those with haplogroup I were particularly vulnerable to HIV infection, the authors state. It took longer time to suppress HIV, and these people showed accelerated progression from HIV state to full-blown AIDS. Mortality from AIDS was also significantly higher in those not belonging to haplogroup I.

But it does not stop with downregulation of adaptive immunity. It upregulates inflammatory response pathways in the immune system cells. This heightened inflammatory response affects cardiovascular system.

Carriers of haplogroup I would have probably arrived from the Middle East around 25,000 years ago and spread throughout Europe, the authors postulate. This is based on the absence of this variant in indigenous populations outside Europe.

The study best fits the north-south gradient in west Europe where death from CAD is much higher in the northern populations in Scandinavia, Germany and the Netherlands. The prevalence of haplogroup I in these countries is 15 per cent to 40 per cent.

However, the prevalence of this variant in people from countries like France, Spain and Switzerland in the south of west Europe is lesser.