The real problem in association studies.
Explore the source record for details and available documents.
Genetic Diseases, Inborn↗
Biomedical subjects
David E Comings
Publications and source records attributed to David E Comings.
Phenylethanolamine N-methyltransferase G-148A genetic variant and weight loss in obese women.
OBJECTIVE: To understand the impact of the phenylethanolamine N-methyltransferase (PNMT) G-148A gene and nutritional variables on weight loss in obese women. RESEARCH METHODS AND PROCEDURES: One hundred forty-nine women, ages 45 to 65 with a body mass index of >30 kg/m(2), participated in a 6-month, open-label intervention that included sibutramine (15 mg/d) and a monthly health-education class. Anthropometric measurements, vital signs, food frequency, exercise log, medication compliance, and psychological and sociological questionnaires were completed each month. Genetic polymorphisms of PNMT were determined. RESULTS: Univariate analysis of G/G, G/A, and A/A genotypes against tertiles of percentage of weight loss were significant at 3 but not at 6 months (Pearson chi(2): p < 0.006; homozygous/heterozygosity: p < 0.002, p < 0.253, and p < 0.122, respectively). A regression model that included the PNMT genetic variation and certain nutrition and exercise variables demonstrated that only the PNMT gene (beta = 0.360, SE 0.585, and p = 0.003) was statistically significant at 6 months, and the total calories (beta = -0.925, SE = 0.004, and p = 0.009), fiber intake (beta = 0.621, SE = 0.124, and p = 0.000), and PNMT (beta = 0.262, SE = 1.415, and p = 0.024) were significant. DISCUSSION: The homozygosity/heterozygosity of the PNMT gene was highly predictive of significant weight loss with sibutramine during the first 3 months, which highlights the need for specific pharmacotherapy. The early weight-loss success of those subjects who were homozygous for PNMT may have motivated and selected those that would make further dietary changes, which then augmented their final weight loss.
Aged↗
22% of preschool children, 8% of primary school students and 3% of adolescents have tics.
Explore the source record for details and available documents.
Comment↗
Association between the low molecular weight cytosolic acid phosphatase gene ACP1*A and comorbid features of Tourette syndrome.
Protein tyrosine phosphatases have been implicated in the regulation of serotonergic and dopaminergic activity in the central nervous system. In a recent study we found that nonA/nonA homozygosity at the locus codifying for the low molecular weight protein tyrosine phosphatase (ACP1) was associated with increased rates of major depression in males (P<0.00003), suggesting that the ACP1*A single nucleotide polymorphism (SNP) may be an important marker for psychopathology. In the present study we examined the ACP1*A SNP in 539 screened controls and 184 male Tourette syndrome (TS) cases, all Caucasians of European descent. The frequency of the nonA allele was markedly increased in TS cases relative to controls (P<0.0005), but this difference was restricted to cases with comorbid attention-deficit hyperactivity disorder (P<0.0001) and conduct disorder (P<0.0002), while having little relevance to TS itself.
Adolescent↗
Association of the muscarinic cholinergic 2 receptor (CHRM2) gene with major depression in women.
Cholinergic neurons have been implicated in depression and in the disorders of REM sleep in depression. We examined a common A-> T 1890 polymorphism in the 3' UTR of the cholinergic muscarinic receptor 2 (CHRM2) gene. There was a significant increase in the frequency of 11 homozygotes in 126 women with major depression (43.7%) compared to 304 women without major depression (25.7%), P =.001. There was no increase in the frequency of 11 homozygotes in 52 men with depression (26.9%) compared to 278 men without depression (27.7%). Regression analysis, scoring subjects with the 11 genotype as 1, and those with other genotypes as 0, showed that in women r(2) =.030, F = 13.37, P =.0003. By contrast, in men r(2) =.00001, F = 0.002, P =.96. These results are consistent with a gender-specific role of the CHRM2 gene in depression in women.
Adult↗
Association between the phenylethanolamine N-methyltransferase gene and multiple sclerosis.
Phenylethanolamine N-methyltransferase (PNMT), the terminal enzyme of the catecholamine biosynthesis pathway, catalyzes the conversion of norepinephrine (NE) to epinephrine (EPI). PNMT is a candidate gene for multiple sclerosis (MS) for two reasons. PNMT is known to map to a region identified in two genome screens for MS and it directly regulates the amounts of NE and EPI, both of which play a significant role in the modulation of the innate immune response. The frequencies of two promoter polymorphisms of the PNMT gene showed genetic association in a case-control study of 108 patients with MS and 774 ethnically and age-matched control subjects. In subjects with MS, significant differences in the frequency of the GG genotype at the G-387A marker and the AA genotype at the G-182A marker were observed. Additionally, when both markers were combined and evaluated, highly significant differences between the polymorphism distributions in patients with MS and control subjects were detected. The data suggest that these promoter polymorphisms of the PNMT gene, both independently and cumulatively, show association with MS.
Adult↗
Association of the acid phosphatase (ACP1) gene with triglyceride levels in obese women.
The acid phosphatase (ACP1) locus codes for a low molecular weight protein tyrosine phosphatase (LMPTP) that is found ubiquitously in human tissues. The *A allele of the ACP1 gene is associated with lower total enzymatic activity than the *B and *C alleles. An association between the *A allele and extreme values of body-mass-index (BMI) and dyslipidemia has previously been described in several samples of obese subjects from the Italian population. In the present study, we investigated the relationship between ACP1 *A allele genotypes (*A/*A, *A/*B, and *A/*C) and non-*A allele genotypes (*B/*B, *B/*C, and *C/*C) and metabolic variables in 277 Caucasian post-menopausal subjects consisting of 82 non-obese subjects (BMI</=29), 60 moderately obese (BMI 30-34) and 135 very obese (BMI>/=35) subjects. ACP1 genotypes were found to be significantly associated with total cholesterol (p</=0.002) and triglyceride (p</=0.001) levels in the obese and very obese women only. The significantly lower levels of triglycerides in *A carriers in this group suggest a protective effect of the *A allele against hypertriglyceridemia. It has been unclear why some individuals who gain weight develop dyslipidemia and other aspects of the metabolic syndrome while others do not. The present study suggests that those who gain weight and carry the ACP1 *A allele may be partially protected against developing the metabolic syndrome. The confirmation of ACP1 as a modifier gene of the metabolic complications could open the door to the prevention of the lethal complications of obesity.
Acid Phosphatase↗
Parent-daughter transmission of the androgen receptor gene as an explanation of the effect of father absence on age of menarche.
Based on an evolutionary theory of socialization, Belsky and colleagues proposed that girls exposed to a stressful environment, especially when due to father absence in the first 7 years of life, showed an early onset of puberty, precocious sexuality, and unstable relationships as adults. The authors of this article examined an alternative explanation that a variant X-linked androgen receptor (AR) gene, predisposing the father to behaviors that include family abandonment, may be passed to their daughters causing early puberty, precocious sexuality, and behavior problems. The results of a study of 121 White males and 164 White females showed a significant association of the short alleles of the GGC repeat polymorphism of the AR gene with a range of measures of aggression and impulsivity, increased number of sexual partners, sexual compulsivity, and lifetime number of sex partners in males; and paternal divorce, father absence, and early age of menarche in females. These findings support a genetic explanation of the Belsky psychosocial evolutionary hypothesis regarding the association of fathers' absence and parental stress with early age of onset of menarche and early sexual activity in their daughters. A genetic explanation of the father absence effect is proposed in which fathers carrying the AR alleles are more likely to abandon a marriage (father absence) and pass those alleles to their daughters in whom they produce an earlier age of menarche and behavioral problems.
Adult↗