دانلود مقاله ISI انگلیسی شماره 33646
عنوان فارسی مقاله

مدارک و شواهد از ارتباط ژنوتیپ KIBRA با حافظه اپیزودیک در خانواده های بیماران روانی و گروه شاهد

کد مقاله سال انتشار مقاله انگلیسی ترجمه فارسی تعداد کلمات
33646 2010 4 صفحه PDF سفارش دهید محاسبه نشده
خرید مقاله
پس از پرداخت، فوراً می توانید مقاله را دانلود فرمایید.
عنوان انگلیسی
Evidence of association of KIBRA genotype with episodic memory in families of psychotic patients and controls
منبع

Publisher : Elsevier - Science Direct (الزویر - ساینس دایرکت)

Journal : Journal of Psychiatric Research, Volume 44, Issue 12, September 2010, Pages 795–798

کلمات کلیدی
حافظه - ارتباط ژنتیک - پلی مورفیسم - اسکیزوفرنی -
پیش نمایش مقاله
پیش نمایش مقاله مدارک و شواهد از ارتباط ژنوتیپ KIBRA با حافظه اپیزودیک در خانواده های بیماران روانی و گروه شاهد

چکیده انگلیسی

The first genome-wide association study of human memory identified an association between a common T/C polymorphism of the KIBRA gene (rs17070145) and episodic memory performance in normal individuals; subsequent studies have implicated the same polymorphism in Alzheimer’s disease. Since impaired neurocognitive performance, including memory, may be both a core feature of schizophrenia and a candidate endophenotype, we attempted to replicate this association in a total sample of 544 subjects (including patients with psychosis, their unaffected relatives as well as normal individuals). In the combined sample there was a significant association between the KIBRA T allele and better performance in the single principle component of the memory measures, which included immediate and delayed logical and visual memory from the Wechsler Memory Scale (p = 0.019). In the unaffected individuals (patients’ relatives and healthy controls) we observed an association of KIBRA with immediate and delayed logical memory (p = 0.020 and 0.025, respectively), while in patients with psychosis with delayed visual memory (p = 0.05). This study replicates the association between the KIBRA gene and episodic memory and suggests a possibly differential effect of the polymorphism in psychotic and non-psychotic individuals.

مقدمه انگلیسی

Human memory is a heritable, polygenic trait. Twin studies have estimated that between 30% and 50% of the variance in performance in memory tasks can be attributed to genetic factors (McClearn et al., 1997 and Thapar et al., 1994). In the first genome-wide association study of memory, Papassotiropoulos et al. identified an association between a common single nucleotide polymorphism (SNP) in the intron 9 of the KIBRA gene (rs17070145) and human episodic memory performance (Papassotiropoulos et al., 2006). The initial findings in a cohort of 351 healthy young Swiss adults were replicated in two independent cognitively normal cohorts, (n = 256 and 424) of European ancestry. Gene expression experiments showed that KIBRA is expressed in the hippocampus and other memory-related brain structures while an fMRI study demonstrated significant KIBRA allele-dependent differences in hippocampal activation, further supporting the role of KIBRA in human memory. The same group recently extended their findings, presenting evidence for association of the same SNP with late-onset Alzheimer’s disease (AD) in two large samples ( Corneveaux et al., 2008). These findings, if confirmed, may have important clinical implications as recent evidence in animal models suggests that the KIBRA gene and the RhoA/ROCK pathway is a possible pharmacological target to treat memory deficits ( Huentelman et al., 2009). The findings of Papassotiropoulos et al. (2006) were replicated in a German sample of 64 healthy elderly subjects, with greater effect sizes (Schaper et al., 2008) and in an Australian sample of 312 adults over the age of 50, attending a memory clinic (Almeida et al., 2008). However, a large study using two different European ancestry cohorts (n = 319 and 365) failed to replicate these findings ( Need et al., 2008), while a recent study from Scotland demonstrated an association of KIBRA specifically with delayed recall of semantically unrelated items ( Bates et al., 2009). Another study that examined a sample of Italian older adults with subjective memory complaints (n = 70) detected a significant association between KIBRA genotype and long-term verbal memory tests, but with the opposite alleles ( Nacmias et al., 2008), while a study of 391 Spanish patients with Alzheimer’s disease (AD) and 428 normal controls again revealed an association with late-onset AD in the opposite direction from the original study ( Rodriguez-Rodriguez et al., 2009). In view of the inconsistency of these findings, further studies are needed to clarify the role of KIBRA polymorphism in the variation of human memory ability. Quite apart from improving our understanding of the biological basis of normal cognition, by identifying the genes that determine cognitive performance, we may also gain valuable insight into disease pathophysiology. Since dementia primarily affects human memory, genes associated with normal memory variation have been examined as risk factors for dementia per se. Furthermore deficits in executive function, learning, and memory may represent candidate endophenotypes for schizophrenia. Studies showing intermediate deficits in attention and memory in patients’ unaffected relatives ( Gur et al., 2007) support their use as potential neurocognitive indices of the genetic liability for schizophrenia. In a recent twin study with structural equation modeling Toulopoulou and colleagues demonstrated that selected neurocognitive measures correlated significantly with schizophrenia and that shared genetic variability explained the majority of the phenotypic correlation between intelligence and schizophrenia ( Toulopoulou et al., 2007). Thus, identifying quantitative trait loci for memory or intelligence may also prove useful in the detection of schizophrenia susceptibility genes. Therefore, we attempted to replicate the association between KIBRA and episodic memory in a sample of healthy individuals, patients with psychosis, and their unaffected relatives.

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